Genomes and Genes
Gene Symbol: SSTR5
Description: somatostatin receptor 5
Alias: SS-5-R, somatostatin receptor subtype 5, somatostatin receptor type 5
Publications144 found, 100 shown here
- Subtypes of the somatostatin receptor assemble as functional homo- and heterodimersM Rocheville
Fraser Laboratories, Departments of Medicine, Pharmacology and Therapeutics, and Neurology and Neurosurgery, McGill University and Royal Victoria Hospital, Montreal, Quebec H3A 1A1, Canada
J Biol Chem 275:7862-9. 2000..Double label confocal fluorescence microscopy showed that when SSTR1 and SSTR5 subtypes were coexpressed in Chinese hamster ovary-K1 cells and treated with agonist they underwent ..
- Role of somatostatin receptor 1 and 5 on epidermal growth factor receptor mediated signalingGeetanjali Kharmate
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada V6T1Z3
Biochim Biophys Acta 1813:1172-89. 2011..We propose that the activation of SSTR and blockade of EGFR might serve novel therapeutic approach in inhibition of tumor proliferation...
- Somatostatin receptors 1 and 5 heterodimerize with epidermal growth factor receptor: agonist-dependent modulation of the downstream MAPK signalling pathway in breast cancer cellsHeather L Watt
Faculty of Medicine, Department of Experimental Medicine, McGill University, Royal Victoria Hospital, Montreal, QC, Canada
Cell Signal 21:428-39. 2009..oestrogen receptor (ER)-positive (MCF-7) or ERalpha-negative (MDA-MB-231) breast cancer cells, we defined SSTR1, SSTR5 and ErbB1 mRNA and protein expression in these two tumour cell lines...
- Identification and characterization of two novel truncated but functional isoforms of the somatostatin receptor subtype 5 differentially present in pituitary tumorsMario Duran-Prado
Department of Cell Biology, Physiology, and Immunology, University of Cordoba, and Centro de Investigacion Biomedica en Red Fisiopatología de la Obesidad y Nutrición, E 14014 Córdoba Spain
J Clin Endocrinol Metab 94:2634-43. 2009..Despite the considerable advances in the knowledge on these receptors and their (patho)physiological roles, there is still evidence that additional receptors for these peptides should exist to fully explain their actions...
- Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activityM Rocheville
Fraser Laboratories, Department of Medicine, McGill University and Royal Victoria Hospital, Montreal, Quebec H3A 1A1, Canada
Science 288:154-7. 2000..Here, we show that dopamine receptor D2R and somatostatin receptor SSTR5 interact physically through hetero-oligomerization to create a novel receptor with enhanced functional activity...
- Association between somatostatin receptor 5 gene polymorphisms and pancreatic cancer risk and survivalDonghui Li
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Cancer 117:2863-72. 2011..Genetic variation in SSTR had been associated with risk of human cancers but had never been investigated in pancreatic cancer...
- Analysis of somatostatin receptors 2 and 5 polymorphisms in patients with acromegalyM Filopanti
Institute of Endocrine Sciences, University of Milan, Ospedale Maggiore Policlinico Mangiagalli e Regina Elena, Istituto di Ricovero e Cura a Curattere Scientifico, Milan, Italy
J Clin Endocrinol Metab 90:4824-8. 2005The aim of the study was to investigate the possible correlation of single nucleotide polymorphisms in somatostatin receptor (SSTR)2 and SSTR5 genes with the responsiveness to somatostatin analogs in a cohort of acromegalic patients.
- A potential inhibitory role for the new truncated variant of somatostatin receptor 5, sst5TMD4, in pituitary adenomas poorly responsive to somatostatin analogsMario Duran-Prado
Department of Cell Biology, Physiology, and Immunology, University of Cordoba, E 14014 Cordoba, Spain
J Clin Endocrinol Metab 95:2497-502. 2010..Recently we identified two novel truncated sst5 variants, sst5TMD5, and sst5TMD4, absent in normal pituitary but expressed in pituitary tumors...
- C-terminal region of human somatostatin receptor 5 is required for induction of Rb and G1 cell cycle arrestK Sharma
Department of Medicine, McGill University and Royal Victoria Hospital, Montreal, Quebec, Canada
Mol Endocrinol 13:82-90. 1999..These data demonstrate that the C-terminal domain of hSSTR5 is required for cytostatic signaling that is PTP dependent and leads to induction of hypophosphorylated Rb and G1 arrest...
- Receptor specific crosstalk and modulation of signaling upon heterodimerization between β1-adrenergic receptor and somatostatin receptor-5Rishi K Somvanshi
Faculty of Pharmaceutical Sciences, Division of Pharmacology and Toxicology, The University of British Columbia, Vancouver, BC, Canada
Cell Signal 23:794-811. 2011..dephosphorylation and nuclear translocation of NFAT, the process predominantly regulated by pJNK in SSTR5 dependent manner...
- The hypofunctional effect of P335L single nucleotide polymorphism on SSTR5 functionGuisheng Zhou
Michael E DeBakey Department of Surgery, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
World J Surg 35:1715-24. 2011b>Somatostatin receptor subtype 5 (SSTR5) mediates the inhibitory effect of somatostatin on insulin expression/secretion and cell proliferation...
- Somatostatin (SRIF) receptor subtype 2 and 5 gene expression in growth hormone-secreting pituitary adenomas: the relationship with endogenous srif activity and response to octreotideCheolyoung Park
Department of Internal Medicine, College of Medicine, Hallym University, Kyunggi, Korea
Endocr J 51:227-36. 2004..However, sst2 and sst5 mRNA levels are not the only factors mediating the response to SRIF...
- Novel polymorphisms in the somatostatin receptor 5 (SSTR5) gene associated with bipolar affective disorderM Nyegaard
Department of Clinical Biochemistry and Genetics, Odense University Hospital, Denmark
Mol Psychiatry 7:745-54. 2002The somatostatin receptor 5 (SSTR5) gene is a candidate gene for bipolar affective disorder (BPAD) as well as for other neuropsychiatric disorders. The gene is positioned on chromosome 16p13...
- Expression of somatostatin receptor types 1-5 in 81 cases of gastrointestinal and pancreatic endocrine tumors. A correlative immunohistochemical and reverse-transcriptase polymerase chain reaction analysisM Papotti
Department of Biomedical Sciences and Oncology, University of Turin, Via Santena 7, 10126 Turin, Italy
Virchows Arch 440:461-75. 2002..Pancreatic insulinomas had an heterogeneous SSTR expression, while 100% of somatostatinomas expressed SSTR5 and 100% gastrinomas and glucagonomas expressed SSTR2...
- Localization of human somatostatin receptor 5 gene (SSTR5) to chromosome band 16p13.3 by fluorescence in situ hybridizationJ Takeda
Department of Medicine, Howard Hughes Medical Institute, University of Chicago, Illinois 60637, USA
Genomics 26:638-9. 1995
- Molecular cloning, functional characterization, and chromosomal localization of a human somatostatin receptor (somatostatin receptor type 5) with preferential affinity for somatostatin-28R Panetta
Fraser Laboratories, Department of Medicine, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada
Mol Pharmacol 45:417-27. 1994..library screening we have cloned a human gene for a subtype of the somatostatin (SST) receptor (SSTR) termed human SSTR5 (hSSTR5), which is located on chromosome 16...
- Mutation of somatostatin receptor type 5 in an acromegalic patient resistant to somatostatin analog treatmentE Ballare
Institute of Endocrine Sciences, University of Milano 20122, Ospedale Maggiore IRCCS, 20122 Milan, Italy
J Clin Endocrinol Metab 86:3809-14. 2001..We suggest that this mutation that abrogates the antiproliferative action of somatostatin and activates mitogenic pathways may be involved in the resistance to somatostatin treatment...
- Cloning, functional expression and pharmacological characterization of a fourth (hSSTR4) and a fifth (hSSTR5) human somatostatin receptor subtypeY Yamada
Department of Metabolism and Clinical Nutrition, Kyoto University Faculty of Medicine, Japan
Biochem Biophys Res Commun 195:844-52. 1993..These results suggest that diverse actions of somatostatin are mediated by at least five somatostatin receptor subtypes with potentially different function...
- The cytoplasmic tail of the human somatostatin receptor type 5 is crucial for interaction with adenylyl cyclase and in mediating desensitization and internalizationN Hukovic
Fraser Laboratories, Department of Medicine, McGill University, Royal Victoria Hospital and the Montreal Neurological Institute, Montreal, Quebec H3A 1A1, Canada
J Biol Chem 273:21416-22. 1998We have investigated the role of the cytoplasmic tail (C-tail) of the human somatostatin receptor type 5 (hSSTR5) in regulating receptor coupling to adenylyl cyclase (AC) and in mediating agonist-dependent desensitization and ..
- BIM-23A760, a chimeric molecule directed towards somatostatin and dopamine receptors, vs universal somatostatin receptors ligands in GH-secreting pituitary adenomas partial responders to octreotideP Jaquet
Interactions Cellulaires Neuroendocriniennes, UMR6544, Centre National de la Recherche Scientifique, Institut Federatif Jean Roche, Faculte de Medecine Nord, Marseille, France
J Endocrinol Invest 28:21-7. 2005We report the comparative efficacy of a somatostatin receptor 1 and 5 subtypes (SSTR2 and SSTR5), and dopamine D2 (DAD2) compound, BIM-23A760, in suppressing GH secretion, in cell culture from human GH-secreting tumors, from patients ..
- Characterization of the intracellular mechanisms mediating somatostatin and lanreotide inhibition of DNA synthesis and growth hormone release from dispersed human GH-secreting pituitary adenoma cells in vitroTullio Florio
Pharmacology and Neuroscience, National Institute for Cancer Research, c o Advanced Biotechnology Center CBA, Genova, Italy
Clin Endocrinol (Oxf) 59:115-28. 2003....
- Gene expression of somatostatin receptor 4 predicts clinical outcome of patients with metastatic neuroendocrine tumors treated with somatostatin analogsOndrej Slaby
Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic
Cancer Biother Radiopharm 25:237-43. 2010..The aim of this study was to quantify expression levels of five SSTR subtypes (SSTR1-SSTR5) and correlate them with the clinical outcomes of patients with NETs who underwent SSA therapy...
- Somatostatin receptor type 5 modulates somatostatin receptor type 2 regulation of adrenocorticotropin secretionAnat Ben-Shlomo
Department of Medicine, Cedars Sinai Research Institute, David Geffen School of Medicine, UCLA, Los Angeles, California 90048, USA
J Biol Chem 280:24011-21. 2005..To assess the contribution of somatostatin receptor subtype 5 (SST5) to somatostatin receptor subtype 2 (SST2) action in these cells, we assessed multipathway ..
- Somatostatin receptor subtypes 2 and 5 mediate inhibition of egg yolk-induced gall bladder emptying in miceP Kaczmarek
Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Interdisziplinares Stoffwechsel Centrum Endokrinologie, Diabetes und Stoffwechsel, Charité Universitätsmedizin 13353 Berlin, Germany
Neurogastroenterol Motil 22:204-9, e66. 2010..Therefore, it is believed that SSTR2 regulates gall bladder contraction; however, evidence has not been provided. Here, we evaluate the effects of SSTR1-SSTR5-selective agonists on egg yolk-induced gall bladder contraction in mice.
- Subtype-selective induction of wild-type p53 and apoptosis, but not cell cycle arrest, by human somatostatin receptor 3K Sharma
Fraser Laboratories for Diabetes Research McGill University and Royal Victoria Hospital Montreal, Quebec, Canada
Mol Endocrinol 10:1688-96. 1996..been reported to follow stimulation of protein tyrosine phosphatase via SSTR2 or inhibition of Ca2+ channels via SSTR5 in heterologous expression systems, the subtype selectivity for signaling apoptosis has not been investigated...
- Characterization of somatostatin receptor subtype-specific regulation of insulin and glucagon secretion: an in vitro study on isolated human pancreatic isletsVandana Singh
Medizinische Klinik m S Hepatologie, Universitatsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany
J Clin Endocrinol Metab 92:673-80. 2007..Five pharmacologically distinct SSTR subtypes are known (SSTR1-SSTR5). In rodents, SSTR2 inhibits glucagon secretion, whereas SSTR5 suppresses the release of insulin...
- [Correlation of somatostatin receptor expression in human hepatocellular carcinoma tissue to serum alpha-fetoprotein concentration]Yong mei Xie
Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P R China
Ai Zheng 26:688-92. 2007..This study was to investigate the expression of SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5 subtypes in HCC, and explore their correlations to serum AFP concentration.
- Somatostatin receptors in primary human breast cancer: quantitative analysis of mRNA for subtypes 1--5 and correlation with receptor protein expression and tumor pathologyU Kumar
Fraser Laboratories for Diabetes Research, Department of Medicine, McGill University, Royal Victoria Hospital, 687 Pine Avenue West, H3A 1A1 Montreal, Quebec, Canada
Breast Cancer Res Treat 92:175-86. 2005..at the mRNA level in breast tumors with 91% of samples showing SSTR1, 98% SSTR2, 96% SSTR3, 76% SSTR4, and 54% SSTR5. SSTR1-5 are localized to both tumor cells and the surrounding peritumoral regions as detected by ..
- SSTR1 and SSTR5 subtypes are the dominant forms of somatostatin receptor in neuroendocrine tumorsHanna Pisarek
Department of Neuroendocrinology, Medical University of Łódź, Poland
Folia Histochem Cytobiol 48:142-7. 2010..The observed pattern suggests that apart from octreotide and lanreotide, newly synthesized multiligand analogs such as SOM 230, KE 108 or SSTR 1 and SSTR 5 selective analogs could be effective in NETs treatment...
- Cloning, expression, pharmacology and tissue distribution of the mouse somatostatin receptor subtype 5H Baumeister
Abteilung Molekulare Genetik, Deutsches Institut für Ernährungsforschung, Potsdam, Germany
J Neuroendocrinol 10:283-90. 1998The gene encoding the mouse somatostatin receptor subtype 5 has been isolated from a genomic library and the mRNA start point mapped to position -95 relative to the translational start codon...
- Oestrogen-mediated regulation of somatostatin receptor expression in human breast cancer cell lines assessed with 99mTc-depreotideB Van Den Bossche
Division of Nuclear Medicine, Ghent University Hospital, De Pintelaan 185, 9000B, Ghent, Belgium
Eur J Nucl Med Mol Imaging 31:1022-30. 2004..Both SSTR2 and SSTR5 were expressed at high levels in T47D cells and ZR75-1 cells...
- Immunohistochemical expression and localization of somatostatin receptor subtypes in prostate cancer with neuroendocrine differentiationD Morichetti
Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy
Int J Immunopathol Pharmacol 23:511-22. 2010..groups; in the latter two, the mean percentages were similar; and (iii) Nuclear staining was seen with SSTR4 and SSTR5; for SSTR4, the mean percentages in the PCa of the three groups were higher than in HGPIN and Nep, the highest ..
- Somatostatin receptors in pituitary and development of somatostatin receptor subtype-selective analogsIlan Shimon
Institute of Endocrinology, Chaim Sheba Medical Center, Tel Hashomer, Israel
Endocrine 20:265-9. 2003Somatostatin receptor (SSTR) subtypes 1, 2, and 5 are expressed in the normal human pituitary. SSTR2 and SSTR5 are expressed in almost all growth hormone (GH) cell adenomas, and prolactin (PRL)-secreting tumors express SSTR5 more than ..
- Somatostatin, but not somatostatin receptor subtypes 2 and 5 selective agonists, inhibits calcitonin secretion and gene expression in the human medullary thyroid carcinoma cell line, TTM C Zatelli
Section of Endocrinology, Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, Via Savonarola 9, 44100 Ferrara, Italy
Horm Metab Res 34:229-33. 2002..are commonly used to treat symptoms in medullary thyroid carcinoma (MTC), that expresses SRIH receptors (SSTR1 to SSTR5), as does the human MTC cell line TT...
- Novel, non-peptidic somatostatin receptor subtype 5 antagonists improve glucose tolerance in rodentsUrs Sprecher
Discovery Research, Chemistry and Non Clinical Safety, F Hoffmann La Roche AG, Grenzacherstrasse 124, CH 4070 Basel, Switzerland
Regul Pept 159:19-27. 2010..We explored the effects of two novel, non-peptidic, orally bioavailable somatostatin receptor subtype 5 antagonists named Compound A and Compound B on glycemia in animal models of type 2 diabetes after an ..
- Identification and characterization of subtype selective somatostatin receptor agonistsS P Rohrer
Department of Endocrinology and Chemical Biology, Merck Research Laboratories, Rahway, NJ 07065, USA
J Physiol Paris 94:211-5. 2000..SSTR2 in inhibition of glucagon release from mouse pancreatic alpha-cells and the somatostatin subtype-5 receptor (SSTR5) as a mediator of insulin secretion from pancreatic beta-cells...
- Cloning of the mouse somatostatin receptor subtype 5 gene: promoter structure and functionD F Gordon
Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Health Sciences Center, Denver 80262, USA
Endocrinology 140:5598-608. 1999..Cloning of the sst5 gene will facilitate the mapping of basal and regulated responses at the transcriptional level...
- Immunohistochemical detection of somatostatin receptor (SSTR) subtypes 2A and 5 in pituitary adenoma from acromegalic patients: good correlation with preoperative response to octreotideMao Takei
Department of Neurosurgery, Nippon Medical School, 1 1 5 Sendagi, Bunkyo ku, Tokyo, 113 8603, Japan
Endocr Pathol 18:208-16. 2007..The aim of this study was to determine the correlation between the expression of somatostatin receptors by immunohistochemistry and the percent suppression of GH levels in the octreotide suppression test...
- Coexpression of somatostatin receptor subtype 5 affects internalization and trafficking of somatostatin receptor subtype 2Nadder Sharif
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada H3A 2B6
Endocrinology 148:2095-105. 2007..These findings indicate that the presence of sst(5) in the same cells modulates trafficking and cell surface regulation of sst(2A) and cellular desensitization to the effects of SRIF...
- Localization and mRNA expression of somatostatin receptor subtypes in human prostatic tissue and prostate cancer cell linesNishtman Dizeyi
Departments of Urology and Pathology, Malmo University Hospital, Lund University, S 205 02 Malmo, Sweden
Urol Oncol 7:91-8. 2002..b>Somatostatin receptor subtype 5 was not detectable...
- Incubation with somatostatin, 5-aza decitabine and trichostatin up-regulates somatostatin receptor expression in prostate cancer cellsZhaoxu Liu
Department of Oncology and Pathology, Karolinska Institute, SE 171 76 Stockholm, Sweden
Oncol Rep 20:151-4. 2008..The inhibition of DNA methylation and histone acetylation resulted in the up-regulation of SSTR5 mRNA expression. The results demonstrate a positive feedback loop between SMS and its receptors...
- Somatostatin stimulates ductal bile absorption and inhibits ductal bile secretion in mice via SSTR2 on cholangiocytesAi Yu Gong
Center for Basic Research in Digestive Diseases, Division of Gastroenterology and Hepatology, Mayo Medical School, Rochester, Minnesota 55905, USA
Am J Physiol Cell Physiol 284:C1205-14. 2003..By RT-PCR, four of five known subtypes of SSTRs (SSTR1, SSTR2A/2B, SSTR3, and SSTR4, but not SSTR5) were detected in cholangiocytes in wild-type mice...
- Somatostatin receptors 1, 2, and 5 cooperate in the somatostatin inhibition of C6 glioma cell proliferation in vitro via a phosphotyrosine phosphatase-eta-dependent inhibition of extracellularly regulated kinase-1/2Federica Barbieri
Laboratory pf Pharmacology, Department of Oncology, Biology, and Genetics, University of Genova, Viale Benedetto XV, 2, 16132 Genova, Italy
Endocrinology 149:4736-46. 2008..SSTR2+5 activation displayed a pattern of response superimposable to that of the SSTR5 agonist alone (low potency and higher efficacy, as compared with BIM-23120)...
- Efficacy of chimeric molecules directed towards multiple somatostatin and dopamine receptors on inhibition of GH and prolactin secretion from GH-secreting pituitary adenomas classified as partially responsive to somatostatin analog therapyP Jaquet
Interactions Cellulaires Neuroendocriniennes, UMR6544, Centre National de la Recherche Scientifique, Institut Federatif Jean Roche, Faculte de Medecine Nord, Boulevard Pierre Dramard, 13916 Marseille Cedex 20, France
Eur J Endocrinol 153:135-41. 2005This study compared the potency of a somatostatin receptor (sstr)2-sstr5 analog, BIM-23244, of an sstr2-dopamine D2 receptor (sstr2-DAD2) molecule, BIM-23A387 and of new somatostatin-dopamine chimeric molecules with differing, enhanced ..
- Efficacy of a dopamine-somatostatin chimeric molecule, BIM-23A760, in the control of cell growth from primary cultures of human non-functioning pituitary adenomas: a multi-center studyTullio Florio
Department of Oncology, Biology and Genetics, University of Genova, Viale Benedetto XV, 2, 16132 Genova, Italy
Endocr Relat Cancer 15:583-96. 2008..Cells were characterized for GH, POMC, sstr1-sstr5, total dopamine D2 receptor (D2R) (in all cases), and D2 receptor long and short isoforms (in 15 out of 38 cases) ..
- Short- and long-term effects of octreotide and SOM230 on GH, IGF-I, ACTH, corticosterone and ghrelin in ratsH A Schmid
Novartis Institutes for BioMedical Research, Oncology Research, Basel, Switzerland
J Endocrinol Invest 28:28-35. 2005..In binding experiments, SOM230 has a higher affinity to SSTR1, SSTR3 and SSTR5 and a slightly lower affinity to SSTR2 compared to octreotide...
- Human somatostatin receptor subtypes in acromegaly: distinct patterns of messenger ribonucleic acid expression and hormone suppression identify different tumoral phenotypesP Jaquet
Interactions Cellulaires Neuroendocrines, UMR 6544, Centre National de la Recherche Scientifique, Institut Federatif Jean Roche, Faculte de Medecine Nord, Marseille, France
J Clin Endocrinol Metab 85:781-92. 2000Recently, studies using somatostatin (SRIF) analogs preferential for either the SRIF receptor 2 (SSTR2) or the SSTR5 subtype demonstrated a variable suppression of GH and PRL release from GH-secreting human adenomas...
- The role of technetium-99m-labeled octreotide acetate scintigraphy in suspected breast cancer and correlates with expression of SSTRFeng Wang
Department of Nuclear Medicine, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing, China
Nucl Med Biol 35:665-71. 2008..To evaluate the value of (99m)Tc-octreotide acetate (hereafter, (99m)Tc-octreotide) somatostatin receptor (SSTR) scintigraphy in the detection of primary breast cancer and to correlate with expression of SSTRs...
- Application of fluorescence recovery after photobleaching to study prestin lateral mobility in the human embryonic kidney cellLouise E Organ
Rice University, Department of Bioengineering, MS 142, P O Box 1892, Houston, Texas 77251 1892, USA
J Biomed Opt 12:021003. 2007..for prestin-green fluorescent protein (GFP) as compared to a control protein, human somatostatin receptor 5 (SSTR5)...
- Radioimmunoassay for somatostatin receptor type 2Y Hirooka
Department of Laboratory Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi, Aichi, 480 1195 Japan
Endocr Regul 35:31-4. 2001..To develop radioimmunoassay for somatostatin receptor type 2 (SSTR2) and search for its presence in certain rat tissues...
- Feedback control of thyrotropin secretion in the chicken: thyroid hormones increase the expression of hypophyseal somatostatin receptor types 2 and 5Bert De Groef
Laboratory of Comparative Endocrinology, Catholic University of Leuven, Naamsestraat 61, B3000 Leuven, Belgium
Gen Comp Endocrinol 152:178-82. 2007We have studied the involvement of the somatostatin receptor type 5 (SSTR5) in the control of thyrotropin (TSH) release in the chicken...
- Somatostatin inhibits insulin and glucagon secretion via two receptors subtypes: an in vitro study of pancreatic islets from somatostatin receptor 2 knockout miceM Z Strowski
Department of Endocrinology and Chemical Biology, Merck Research Laboratories, Rahway, New Jersey 07065, USA
Endocrinology 141:111-7. 2000..Five distinct membrane receptors (SSTR1-5) for SST are known, and at least two (SSTR2 and SSTR5) have been proposed to regulate pancreatic endocrine function...
- Imaging of neuroendocrine tumours with gamma-emitting radiopharmaceuticalsE Bombardieri
Division of Nuclear Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Q J Nucl Med Mol Imaging 54:3-15. 2010..The subtypes sstr2 and sstr5 are the most commonly expressed in NETs...
- Relationship between somatostatin receptor subtype expression and clinicopathology, Ki-67, Bcl-2 and p53 in colorectal cancerCheng Zhi Qiu
Department of General Surgery, Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian Province, China
World J Gastroenterol 12:2011-5. 2006..To study the SSTR1, 2, 3, 4, 5 expression and their relationships with clinico-pathological factors, cell proliferation, Bcl-2 and p53 expression in colorectal cancer cells...
- The levels of somatostatin receptors in causative tumors of oncogenic osteomalacia are insufficient for their agonist to normalize serum phosphate levelsAkira Ishii
Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, 1 4 3 Asahi machi, Abeno Ku, Osaka, Japan
Calcif Tissue Int 86:455-62. 2010..The mean expression levels of SSTR1, SSTR3, and SSTR5 were similar in the OOM and non-OOM tumors...
- The tuberin (TSC2), autosomal dominant polycystic kidney disease (PKD1), and somatostatin type V receptor (SSTR5) genes form a synteny group in the Fugu genomeR Sandford
Department of Medicine, Addenbrookes Hospital, Cambridge, England, United Kingdom
Genomics 38:84-6. 1996..In addition sequences homologous to the somatostatin type V receptor (SSTR5) were identified 5' to PKD1, defining a larger syntenic region, as this gene has also been mapped to human ..
- Identification of ciliary localization sequences within the third intracellular loop of G protein-coupled receptorsNicolas F Berbari
Department of Pharmacology, Division of Human Genetics, and College of Medicine, The Ohio State University, Columbus, OH 43210, USA
Mol Biol Cell 19:1540-7. 2008..this hypothesis we expressed chimeric receptors containing fragments of Sstr3 and Htr6 in the nonciliary receptors Sstr5 and Htr7, respectively, in ciliated cells...
- Acromegaly in a patient with normal pituitary gland and somatotropic adenoma located in the sphenoid sinusMaria Kurowska
Department of Endocrinology, Medical University, Lublin, Poland
Endokrynol Pol 59:348-51. 2008..somatotropic pituitary adenoma: GH(+), PRL(-), ACTH(-), TSH(-), FSH(-), LH(-), MIB1 < 1%, SSTR3(+) and SSTR5(+). Post-surgical evaluation showed normal pituitary MRI scans, GH and IGF-1 levels 0...
- 111In-DTPA-D-Phe1-octreotide binding and somatostatin receptor subtypes in thyroid tumorsE B Forssell-Aronsson
Department of Radiation Physics, Sahlgrenska University Hospital, Goteborg University, Sweden
J Nucl Med 41:636-42. 2000..The purpose of this study was to evaluate the potential for therapy of thyroid tumors using the radiolabeled somatostatin (SS) analog octreotide...
- Benzoxazole piperidines as selective and potent somatostatin receptor subtype 5 antagonistsRainer E Martin
F Hoffmann La Roche Ltd, Pharmaceuticals Division, Medicinal Chemistry, CH 4070 Basel, Switzerland
Bioorg Med Chem Lett 19:6106-13. 2009....
- Somatostatin receptor subtypes mRNA in TSH-secreting pituitary adenomas: a case showing a dramatic reduction in tumor size during short octreotide treatmentKazuhiko Horiguchi
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan
Endocr J 54:371-8. 2007..In comparison to the normal pituitary, sstr2A>sstr1>sstr5>sstr3 mRNAs were expressed in the TSH-secreting adenomas examined...
- Neuroendocrine tumors and somatostatin: imaging techniquesW W de Herder
Section of Endocrinology, Department of Internal Medicine, Erasmus Rotterdam, The Netherlands
J Endocrinol Invest 28:132-6. 2005Tumors and metastases bearing the somatostatin receptor subtypes 2 (SSTR2) or SSTR5 can be visualized in vivo after injection of radiolabeled octapeptide somatostatin analogs like 111In-pentetreotide...
- Somatostatinergic ligands in dopamine-sensitive and -resistant prolactinomasAlessandra Fusco
Interactions Cellulaires Neuroendocrinnienes, UMR CNRS 6544, Faculte de Medecine Nord, University of Aix Marseilles II, Boulevard Pierre Dramard, 13015, Marseilles, France
Eur J Endocrinol 158:595-603. 2008..Prolactinomas express somatostatin (SST) receptor subtypes, SSTR1, 2, and 5. The aim of this study was to determine whether different SST compounds could overcome the resistance to DA in prolactinomas...
- Phosphorylation of threonine 333 regulates trafficking of the human sst5 somatostatin receptorAline Petrich
Department of Pharmacology and Toxicology, Jena University Hospital Friedrich Schiller University Jena, Drackendorfer Strasse 1, D 07749 Jena, Germany
Mol Endocrinol 27:671-82. 2013..In addition, we identify G protein-coupled receptor kinase 2-mediated phosphorylation and protein phosphatase 1γ-mediated dephosphorylation of T333 as key regulators of rapid internalization and recycling of the human sst5 receptor...
- Acromegaly: molecular expression of somatostatin receptor subtypes and treatment outcomeMarcello D Bronstein
Neuroendocrine Unit, Division of Endocrinology and Metabolism, Hospital das Clinicas, University of Sao Paulo Medical School, Av 9 de Julho 3858, 01406 100 Sao Paulo, Brazil
Front Horm Res 35:129-34. 2006..There are five known SSTR subtypes. SSTR2 and SSTR5 are usually expressed in GH-secreting pituitary tumors, and both octreotide and lanreotide bind preferentially to ..
- Expression pattern of somatostatin receptor subtypes 1-5 in human skin: an immunohistochemical study of healthy subjects and patients with psoriasis or atopic dermatitisLena Hagströmer
Section of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden
Exp Dermatol 15:950-7. 2006..in the papillary and upper reticular dermis, showed a strong expression of SSTR1-4, but a weak expression of SSTR5. SSTR1-5 were strongly expressed in the sweat glands in all skin biopsies...
- Identification of somatostatin receptors controlling growth hormone and thyrotropin secretion in the chicken using receptor subtype-specific agonistsK L Geris
Laboratory of Comparative Endocrinology, Katholieke Universiteit Leuven, Naamsestraat 61, B 3000 Leuven, Belgium
J Endocrinol 177:279-86. 2003..Our data have indicated that SRIH inhibits chicken pituitary function through sstr2 and sstr5. Only sstr2 seems to be involved in the control of chicken GH release, whereas both sstr2 and sstr5 inhibit ..
- NODAGATOC, a new chelator-coupled somatostatin analogue labeled with [67/68Ga] and [111In] for SPECT, PET, and targeted therapeutic applications of somatostatin receptor (hsst2) expressing tumorsKlaus Peter Eisenwiener
Division of Radiological Chemistry, Institute of Nuclear Medicine, Department of Radiology, University Hospital, Petersgraben 4, CH 4031 Basel, Switzerland
Bioconjug Chem 13:530-41. 2002..111In]-NODAGATOC shows 2 times higher binding affinity to sstr2, but also a factor of 4 higher affinity to sstr5 compared to [67Ga]-NODAGATOC. [67Ga]-NODAGATOC is very stable in serum and rat liver homogenate...
- Perspectives of new potential therapeutic applications of somatostatin analogsMarek Pawlikowski
Department of Experimental Endocrinology and Hormone Diagnostics, Institute of Endocrinology, Medical University of Lodz, Dr Sterling Str No 3, 91 425 Lodz, Poland
Neuro Endocrinol Lett 24:21-7. 2003..g. prostatic cancers) or SSTR5 (e.g. colonic cancers)...
- Somatostatin inhibits insulin release via SSTR2 in hamster clonal beta-cells and pancreatic isletsCheng Yu Yao
Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, USA
Regul Pept 129:79-84. 2005Somatostatin (SST) inhibits pancreatic endocrine secretion. It is generally accepted that SSTR2 and SSTR5 mediate the inhibition of glucagon and insulin release, respectively...
- Transcriptional and pathway analysis in the hypothalamus of newly hatched chicks during fasting and delayed feedingStacy E Higgins
Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA
BMC Genomics 11:162. 2010..Results confirmed functional relationships among members of the predicted gene network. Moreover, the effects observed were dependent upon the nutritional state of the animals (fed vs. fasted)...
- Double-gene ablation of SSTR1 and SSTR5 results in hyperinsulinemia and improved glucose tolerance in miceX P Wang
Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, Tex, USA
Surgery 136:585-92. 2004..The objective of this study was to determine the effect of double-gene ablation of SSTR1 and SSTR5 on insulin secretion and glucose homeostasis in mice.
- Differential molecular mechanism of docetaxel-octreotide combined treatment according to the docetaxel-resistance status in PC3 prostate cancer cellsLaura Lattanzio
Laboratory of Cancer Genetics and Translational Oncology, Oncology Department, S Croce General Hospital, Cuneo, Italy
Anticancer Drugs 24:120-30. 2013..P-glycoprotein function was examined together with the modulation of SST receptors type 2 and 5 (SSTR2 and SSTR5)...
- Truncated variants of pig somatostatin receptor subtype 5 (sst5) act as dominant-negative modulators for sst2-mediated signalingMario Duran-Prado
Department of Cell Biology, Physiology, and Immunology, University of Cordoba, Reina Sofia University Hospital, Instituto Maimonides de Investigacion Biomedica de Cordoba, and CIBER Fisiopatologia de la Obesidad y Nutricion, Cordoba, Spain
Am J Physiol Endocrinol Metab 303:E1325-34. 2012....
- Pasireotide is more effective than octreotide in reducing hepatorenal cystogenesis in rodents with polycystic kidney and liver diseasesTatyana V Masyuk
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
Hepatology 58:409-21. 2013..Expression of SSTR1 and SSTR2 (but not SSTR3 and SSTR5) was decreased in cystic cholangiocytes compared to control...
- Expression of Ki-67, PTTG1, FGFR4, and SSTR 2, 3, and 5 in nonfunctioning pituitary adenomas: a high throughput TMA, immunohistochemical studyClaudia Ramirez
Endocrinology Service, Experimental Endocrinology Unit, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social IMSS, 11560 México City, Mexico
J Clin Endocrinol Metab 97:1745-51. 2012..Nonfunctioning pituitary adenomas (NFPA) are the most common pituitary neoplasms. There is no clinical, biochemical, or histopathological marker that would accurately predict recurrence of NFPA...
- Radiolabeled peptides in diagnosis and tumor imaging: clinical overviewRichard R P Warner
Division of Gastroenterology, Department of Medicine, The Mount Sinai School of Medicine, Weill Medical College of Cornell University, New York, NY, USA
Semin Nucl Med 32:79-83. 2002..Labeled octreotide and the other two analogues have a strong affinity for SSTR2 and SSTR5, which thereby produce positive imaging...
- Differential expression of somatostatin receptors 1-5 in neuroendocrine carcinoma of the lungKoji Tsuta
Department of Pathology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
Pathol Res Pract 208:470-4. 2012..6%), 40/56 (69%), 14/56 (24.1%), 9/56 (15.5%), 0/58, and 2/55 (3.4%) cases, respectively. Except for SSTR5, all SSTRs showed a tendency toward decreased expression in well- to poorly differentiated NECs...
- Immunohistochemical distribution of somatostatin and somatostatin receptor subtypes (SSTR1-5) in hypothalamus of ApoD knockout mice brainUjendra Kumar
The University of British Columbia, Vancouver, BC V6T 1Z3, Canada
J Mol Neurosci 48:684-95. 2012..b>SSTR5 is well expressed in ventromedial and arcuate nucleus whereas weakly expressed in paraventricular nucleus...
- A 12-month phase 3 study of pasireotide in Cushing's diseaseAnnamaria Colao
Department of Molecular and Clinical Endocrinology and Oncology, Section of Endocrinology, University of Naples Federico II, Naples, Italy
N Engl J Med 366:914-24. 2012..Cushing's disease is associated with high morbidity and mortality. Pasireotide, a potential therapy, has a unique, broad somatostatin-receptor-binding profile, with high binding affinity for somatostatin-receptor subtype 5...
- [Tumor growth inhibition of paclitaxel-octreotide conjugates on human non small cell lung cancer: experiment with mice]Hong Chang Shen
Department of Oncology, Qilu Hospital, Shandong University, Jinan 250012, China
Zhonghua Yi Xue Za Zhi 88:2498-503. 2008..To evaluate the antitumor effects of the conjugates synthesized by coupling cytotoxic paclitaxel (PTX) to somatostatin analog octreotide (OCT) on human non small cell lung cancer (NSCLC)...
- Amplification of agonist stimulation of human G-protein-coupled receptor signaling in yeastNobuo Fukuda
Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, Nada Ku, Kobe 657 8501, Japan
Anal Biochem 417:182-7. 2011..We chose human somatostatin receptor subtype 5 (hSSTR5) as a model of a human GPCR...
- Somatostatin receptors subtypes 2 and 5, dopamine receptor type 2 expression and gsp status as predictors of octreotide LAR responsiveness in acromegalyLeonardo Vieira Neto
Hospital Universitario Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, RJ, Brazil
Arq Bras Endocrinol Metabol 52:1288-95. 2008..We present two acromegalic patients in which clinical and molecular data are discussed in regard to their ability to predict long term octreotide LAR therapy response...
- Gene expression of somatostatin receptor subtypes SSTR2a, SSTR3 and SSTR5 in peripheral blood of neuroendocrine lung cancer affected patientsLucia Anna Muscarella
Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Foggia, Italy
Cell Oncol (Dordr) 34:435-41. 2011..Short peptide analogues demonstrate specific binding only for the subgroup consisting of SSTR2a, SSTR3 and SSTR5. Moreover, previous studies reported that expression of mRNA for SSTR2a correlated with therapeutic outcome in ..
- Restricted expression of somatostatin receptor 3 to primary cilia in the pancreatic islets and adenohypophysis of miceToshihiko Iwanaga
Laboratory of Histology and Cytology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Biomed Res 32:73-81. 2011..Since the somatostatin inhibition of both insulin and GH release is regulated mainly by SSTR1 and SSTR5, the primary cilia expressing SSTR3 may be involved in a signaling which differs from that via other SSTR subtypes ..
- Somatostatin receptor subtype expression in human thyroid tumoursA Klagge
Department of Internal Medicine, Division of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany
Horm Metab Res 42:237-40. 2010..thyroid tumours, benign neoplasia, and normal surrounding tissue with a predominant expression of SSTR2 and SSTR5, and a weak expression of SSTR1 and SSTR3. Weak SSTR4 mRNA expression was detected in some PTCs...
- Somatostatin receptor subtypes in hormone-refractory (castration-resistant) prostatic carcinomaRoberta Mazzucchelli
Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona 60126, Italy
Asian J Androl 13:242-7. 2011..all five SSTRs were expressed), membrane (only SSTR3 and SSTR4 were expressed) and nuclei (only SSTR4 and SSTR5 were expressed) of the glands in HR PCa were 20-70% lower than in the other two groups, the differences being ..
- Importance of asparagine residues at positions 13 and 26 on the amino-terminal domain of human somatostatin receptor subtype-5 in signallingShota Togawa
Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, Kobe, Japan
J Biochem 147:867-73. 2010..These results clearly show the importance of these asparagine residues in the agonist-specific signalling of hSSTR5, although it was not enough to identify the consequence of oligosaccharides...
- Clinicopathological characterization of TSH-producing adenomas: special reference to TSH-immunoreactive but clinically non-functioning adenomasElaine Lu Wang
Department of Human Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto Cho, Tokushima 770 8503, Japan
Endocr Pathol 20:209-20. 2009..Membranous somatostatin receptor (SSTR)-2A immunoreactivity was found in 89% STAs and 94% FTSHomas, whereas SSTR5 was positive in 78% of both STAs and FTSHomas...
- Overexpression and functional relevance of somatostatin receptor-1, -2, and -5 in endometrium and endometriotic lesionsAlessandro Fasciani
Ospedali Galliera, Genova, Italy
J Clin Endocrinol Metab 95:5315-9. 2010..Five subtypes of somatostatin receptors have been identified, and the therapeutic use of somatostatin receptor-selective agonists has been reported in several diseases...
- The role of G-proteins in the dimerisation of human somatostatin receptor types 2 and 5Michael Grant
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
Regul Pept 159:3-8. 2010..the coupling of G-protein as a contributing factor in the homo- and heterodimerisation of human (h) SSTR2 and SSTR5. When cells stably expressing hSSTR2 are pretreated with pertussis toxin (PTX), dissociation of hSSTR2 dimers ..
- Co-expression of somatostatin receptor subtypes and estrogen receptor-α mRNAs by non-functioning pituitary adenomas in young patientsHiroshi Nishioka
Department of Neurosurgery, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan
Mol Cell Endocrinol 331:73-8. 2011..NFomas expressed higher levels of SSTR3 than functioning adenomas but had lower levels of SSTR2, SSTR5 and D2R mRNAs than GHomas. Their ERα levels were higher than those of GHomas...
- Somatostatin analogues inhibit cancer cell proliferation in an SSTR2-dependent manner via both cytostatic and cytotoxic pathwaysYi Zou
School of Life Science and Technology, Jinan University, Guangzhou 510632, People s Republic of China
Oncol Rep 21:379-86. 2009..Octreotide and RC-160 (vapreotide) are two well tolerated SSTR2/SSTR5 selective somatostatin analogues (SSA) that have been used in the treatment of cancers with mixed outcomes...
- Identification of the transgenic integration site in immunodeficient tgε26 human CD3ε transgenic miceIzumi Ohigashi
Division of Experimental Immunology, Institute for Genomic Research, University of Tokushima, Tokushima, Japan
PLoS ONE 5:e14391. 2010..We found that multiple copies of the human CD3ε transgene are inserted between the Sstr5 and Metrn loci on chromosome 17, and that this is accompanied by duplication of the neighboring genomic region ..
- Microarray analysis of somatostatin receptor 5-regulated gene expression profiles in murine pancreasSanjeet G Patel
The Michael E DeBakey Department of Surgery, Baylor College of Medicine, 1709 Dryden Street, Suite 1500, Houston, TX 77030, USA
World J Surg 33:630-7. 2009We previously demonstrated that somatostatin receptor type 5 (SSTR5) gene ablation results in alterations in insulin secretion and glucose metabolism, accompanied by morphologic alterations in the islets of Langerhans...
- Quantitative analysis of somatostatin receptor subtypes (1-5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LARGiselle F Taboada
Endocrinology Section, Radiology Section, Neurosurgery Section and Pathology Section, Hospital Universitario Clementino Fraga Filho, Instituto de Biofisica Carlos Chagas Filho, Federal University of Rio de Janeiro, 21941 913, Rio de Janeiro, Brazil
Eur J Endocrinol 158:295-303. 2008..To determine whether the somatostatin receptor subtype (SSTR) expression profile correlates with hormonal and tumor volume responses to postsurgical octreotide long acting repeatable (OCT LAR) treatment...
- Pre-clinical and clinical experiences with novel somatostatin ligands: advantages, disadvantages and new prospectsL J Hofland
Department of Internal Medicine, Section Endocrinology, Erasmus MC, Rotterdam, The Netherlands
J Endocrinol Invest 28:36-42. 2005..GH-secreting pituitary adenomas preferentially express SSTR2 and SSTR5, prolactinomas SSTR1 and SSTR5, and corticotroph adenomas express SSTR2 (low number) and predominantly SSTR5s...
- [Expression of somatostatin receptor reporter gene and its correlation with targeted imaging in vivo for detection of pancreas carcinoma]Zi zheng Wang
Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing 210006, China
Zhonghua Zhong Liu Za Zhi 27:663-6. 2005..To evaluate the value of (99 m)Tc-sandostatin scintigraphy in targeted diagnosis of pancreas carcinoma and the correlation with expression of somatostatin receptor (SSTR) reporter gene in tumor tissue...
- Messenger RNA expression of somatostatin receptor subtypes in human and rat gastric mucosaeM Le Romancer
Unité de Recherches Biologie et Pathogie de l Epithelium Digestif, Paris, France
Life Sci 58:1091-8. 1996..fundic mucosal cells allowed us to localize SSTR2-5 in the parietal cell-enriched fraction, whereas SSTR2 and SSTR5 were the only subtypes found in the endocrine cell-enriched fraction...
- Octreotide inhibits proliferation and induces apoptosis of hepatocellular carcinoma cellsHai Lin Liu
Department of Gastroenterology, The Ninth People Hospital, Shanghai Second Medical University, Shanghai 200011, China
Acta Pharmacol Sin 25:1380-6. 2004..To study the effect of octreotide on cell proliferation and apoptosis in different hepatocellular carcinoma (HCC) cells and hepatocytes...
- Regulation of Mouse Somatostatin Receptor Subtype 5 GeneWHITNEY WOODMANSEE; Fiscal Year: 2004..is to expand our understanding of the basic molecular mechanism(s) regulating expression of the mouse somatostatin receptor subtype 5 gene (sst5)...
- Intraislet Communication in Surgically-Altered PancreasFRANCIS BRUNICARDI; Fiscal Year: 2007..subtypes responsible for the inhibition of insulin are unknown, however, preliminary data suggest that SSTR1 and SSTR5 are important regulators of insulin secretion and that there are species differences...
- PHARMACOLOGY OF SOMATOSTATIN RECEPTORSJean Rivier; Fiscal Year: 1999..and antagonist to each of the five recently discovered and cloned receptor subtypes SSTR1, SSTR2, SSTR3, SSTR4 and SSTR5. This area of research is highly desired since selective and potent SRIF analogs are needed as tools to unravel ..
- Somatostatin Receptor Subtype 5 Regulation of Islet NeoplasiaFRANCIS CHARLES BRUNICARDI; Fiscal Year: 2010..our SSTR5-/- mice develop INeo associated with hyperinsulinemia, hypoglycemia and PDX-1 overexpression, suggesting mSSTR5 ..
- Molecular Epidemiology of Pancreatic CancerDonghui Li; Fiscal Year: 2008..Such information will be valuable for the primary prevention of this deadly disease. ..