prostacyclin receptor

Summary

Gene Symbol: prostacyclin receptor
Description: prostaglandin I2 receptor
Alias: PRIPR, prostacyclin receptor, PGI receptor, PGI2 receptor, prostaglandin I2 (prostacyclin) receptor (IP), prostanoid IP receptor
Species: human
Products:     prostacyclin receptor

Top Publications

  1. Smyth E, Austin S, Reilly M, Fitzgerald G. Internalization and sequestration of the human prostacyclin receptor. J Biol Chem. 2000;275:32037-45 pubmed
  2. Zhang Z, Austin S, Smyth E. Glycosylation of the human prostacyclin receptor: role in ligand binding and signal transduction. Mol Pharmacol. 2001;60:480-7 pubmed
    ..Our findings demonstrate greater glycosylation at N(78) compared with N(7). The extent of N-linked glycosylation of hIP may be important for membrane localization, ligand binding, and signal transduction. ..
  3. Stitham J, Gleim S, Douville K, Arehart E, Hwa J. Versatility and differential roles of cysteine residues in human prostacyclin receptor structure and function. J Biol Chem. 2006;281:37227-36 pubmed
    ..Here we report distinctive roles for extracellular- and transmembrane-located cysteine residues in human prostacyclin receptor structure-function...
  4. Arehart E, Stitham J, Asselbergs F, Douville K, MacKenzie T, Fetalvero K, et al. Acceleration of cardiovascular disease by a dysfunctional prostacyclin receptor mutation: potential implications for cyclooxygenase-2 inhibition. Circ Res. 2008;102:986-93 pubmed publisher
    ..Using a naturally occurring mutation in the prostacyclin receptor, we report for the first time that a deficiency in prostacyclin signaling through its G protein-coupled ..
  5. Stitham J, Arehart E, Elderon L, Gleim S, Douville K, Kasza Z, et al. Comprehensive biochemical analysis of rare prostacyclin receptor variants: study of association of signaling with coronary artery obstruction. J Biol Chem. 2011;286:7060-9 pubmed publisher
    ..Using human population-based studies (n = 1,761) to search for dysfunctional human prostacyclin receptor (hIP) variants, we recently discovered 18 non-synonymous mutations, all with frequencies less than 2% in ..
  6. Patrignani P, Di Febbo C, Tacconelli S, Douville K, Guglielmi M, Horvath R, et al. Differential association between human prostacyclin receptor polymorphisms and the development of venous thrombosis and intimal hyperplasia: a clinical biomarker study. Pharmacogenet Genomics. 2008;18:611-20 pubmed publisher
    ..i) differences on systemic markers of vascular disease and platelet activation and (ii) the influence of prostacyclin receptor gene (PTGIR) polymorphisms...
  7. Turner E, Kinsella B. Estrogen increases expression of the human prostacyclin receptor within the vasculature through an ERalpha-dependent mechanism. J Mol Biol. 2010;396:473-86 pubmed publisher
    Prostacyclin and the prostacyclin receptor (IP) are implicated in mediating many of the atheroprotective effects of estrogen in both humans and in animal models but through unknown mechanisms...
  8. Miggin S, Lawler O, Kinsella B. Investigation of a functional requirement for isoprenylation by the human prostacyclin receptor. Eur J Biochem. 2002;269:1714-25 pubmed
    In the current study, we have established that the human (h) prostacyclin receptor (IP) is isoprenylated in whole cells...
  9. Stitham J, Stojanovic A, Hwa J. Impaired receptor binding and activation associated with a human prostacyclin receptor polymorphism. J Biol Chem. 2002;277:15439-44 pubmed
    The human prostacyclin receptor (hIP) is a seven transmembrane-spanning G-protein-coupled receptor that plays an important role in vascular homeostasis...

More Information

Publications96

  1. Lawler O, Miggin S, Kinsella B. Protein kinase A-mediated phosphorylation of serine 357 of the mouse prostacyclin receptor regulates its coupling to G(s)-, to G(i)-, and to G(q)-coupled effector signaling. J Biol Chem. 2001;276:33596-607 pubmed
    The prostacyclin receptor (IP) is primarily coupled to G alpha(s)-dependent activation of adenylyl cyclase; however, a number of studies indicate that the IP may couple to other secondary effector systems perhaps in a species-specific ..
  2. Stitham J, Stojanovic A, Ross L, Blount A, Hwa J. Clusters of transmembrane residues are critical for human prostacyclin receptor activation. Biochemistry. 2004;43:8974-86 pubmed
    ..These critical residues localized to four distinct clusters (analysis via a rhodopsin-based human prostacyclin receptor homology model). Residues Y75(2.65) (TMII), F95(3.28) (TMIII), and R279(7...
  3. O Meara S, Kinsella B. The effect of the farnesyl protein transferase inhibitor SCH66336 on isoprenylation and signalling by the prostacyclin receptor. Biochem J. 2005;386:177-89 pubmed
    Like Ras, farnesylation of the IP (prostacyclin receptor) is required for its efficient intracellular signalling, and hence the IP represents a potential target for inhibition by FTIs [FTase (farnesyl protein transferase) inhibitors]...
  4. Wikström K, Reid H, Hill M, English K, O Keeffe M, Kimbembe C, et al. Recycling of the human prostacyclin receptor is regulated through a direct interaction with Rab11a GTPase. Cell Signal. 2008;20:2332-46 pubmed publisher
    The human prostacyclin receptor (hIP) undergoes agonist-induced internalization but the mechanisms regulating its intracellular trafficking and/or recycling to the plasma membrane are poorly understood...
  5. O Keeffe M, Reid H, Kinsella B. Agonist-dependent internalization and trafficking of the human prostacyclin receptor: a direct role for Rab5a GTPase. Biochim Biophys Acta. 2008;1783:1914-28 pubmed publisher
    The human prostacyclin receptor (hIP) undergoes rapid agonist-induced internalization by largely unknown mechanism(s)...
  6. Stitham J, Arehart E, Gleim S, Li N, Douville K, Hwa J. New insights into human prostacyclin receptor structure and function through natural and synthetic mutations of transmembrane charged residues. Br J Pharmacol. 2007;152:513-22 pubmed
    The human prostacyclin receptor (hIP), a G-protein coupled receptor (GPCR) expressed mainly on platelets and vascular smooth muscle cells, plays important protective roles in the cardiovascular system...
  7. Stitham J, Arehart E, Gleim S, Douville K, MacKenzie T, Hwa J. Arginine (CGC) codon targeting in the human prostacyclin receptor gene (PTGIR) and G-protein coupled receptors (GPCR). Gene. 2007;396:180-7 pubmed
    The human prostacyclin receptor (hIP) has recently been recognized as an important seven transmembrane G-protein coupled receptor that plays critical roles in atheroprevention and cardioprotection...
  8. Smyth E, Austin S, Fitzgerald G. Activation-dependent internalization of the human prostacyclin receptor. Adv Exp Med Biol. 2002;507:295-301 pubmed
  9. Wilson S, Smyth E. Internalization and recycling of the human prostacyclin receptor is modulated through its isoprenylation-dependent interaction with the delta subunit of cGMP phosphodiesterase 6. J Biol Chem. 2006;281:11780-6 pubmed
    ..Recycling of IP, but not IPSSLC, upon agonist removal was facilitated by overexpression of PDE6delta. Thus PDE6delta interacts specifically with IP to modulate receptor trafficking. ..
  10. Stitham J, Stojanovic A, Merenick B, O Hara K, Hwa J. The unique ligand-binding pocket for the human prostacyclin receptor. Site-directed mutagenesis and molecular modeling. J Biol Chem. 2003;278:4250-7 pubmed
    The human prostacyclin receptor is a seven-transmembrane alpha-helical G-protein coupled receptor, which plays important roles in both vascular smooth muscle relaxation as well as prevention of blood coagulation...
  11. Hayes J, Lawler O, Walsh M, Kinsella B. The prostacyclin receptor is isoprenylated. Isoprenylation is required for efficient receptor-effector coupling. J Biol Chem. 1999;274:23707-18 pubmed
    The prostacyclin receptor (IP), a G protein-coupled receptor, mediates the actions of the prostanoid prostacyclin and its mimetics...
  12. Smyth E, Li W, Fitzgerald G. Phosphorylation of the prostacyclin receptor during homologous desensitization. A critical role for protein kinase c. J Biol Chem. 1998;273:23258-66 pubmed
    Agonist-induced phosphorylation of an epitope-tagged prostacyclin receptor (HAhIP) is mediated primarily by PKC (Smyth, E. M., Nestor, P. V., and FitzGerald G. A. (1996) J. Biol. Chem. 271, 33698-33704)...
  13. Giguere V, Gallant M, de Brum Fernandes A, Parent J. Role of extracellular cysteine residues in dimerization/oligomerization of the human prostacyclin receptor. Eur J Pharmacol. 2004;494:11-22 pubmed
    ..The prostanoid IP receptor is a G-protein-coupled receptor...
  14. Adderley S, Sprague R, Stephenson A, Hanson M. Regulation of cAMP by phosphodiesterases in erythrocytes. Pharmacol Rep. 2010;62:475-82 pubmed
    ..In erythrocytes activation of either beta adrenergic receptors (beta(2)AR) or the prostacyclin receptor (IPR) results in increases in cAMP and ATP release...
  15. Stitham J, Hwa J. Prostacyclin, Atherothrombosis and Diabetes Mellitus: Physiologic and Clinical Considerations. Curr Mol Med. 2016;16:328-42 pubmed
    ..A growing body of evidence from randomized controlled trials, studies of human prostacyclin receptor (hIP) variants, and IP-receptor knockout studies in mice has shown that PGI2 may have a protective effect ..
  16. Sommer N, Richter M, Tello K, Grimminger F, Seeger W, Ghofrani H, et al. [Update pulmonary arterial hypertension : Definitions, diagnosis, therapy]. Internist (Berl). 2017;58:937-957 pubmed publisher
    ..as well as with more novel substances, such as a soluble guanylyl cyclase stimulator and an oral prostacyclin receptor agonist...
  17. Lewis D, Canzoneri B, Gu Y, Zhao S, Wang Y. Maternal levels of prostacyclin, thromboxane, ICAM, and VCAM in normal and preeclamptic pregnancies. Am J Reprod Immunol. 2010;64:376-83 pubmed publisher
    ..In contrast, maternal ICAM and VCAM levels were not different between the two groups. These data suggest that serum ICAM and VCAM levels may not be sensitive inflammatory biomarkers for preeclampsia. ..
  18. Knebel S, Sprague R, Stephenson A. Prostacyclin receptor expression on platelets of humans with type 2 diabetes is inversely correlated with hemoglobin A1c levels. Prostaglandins Other Lipid Mediat. 2015;116-117:131-5 pubmed publisher
    ..Activation of the platelet prostacyclin receptor (IPR) results in cAMP accumulation and inhibition of platelet aggregation...
  19. Kaufmann P, Niglis S, Bruderer S, Segrestaa J, Äänismaa P, Halabi A, et al. Effect of lopinavir/ritonavir on the pharmacokinetics of selexipag an oral prostacyclin receptor agonist and its active metabolite in healthy subjects. Br J Clin Pharmacol. 2015;80:670-7 pubmed publisher
    ..Therefore, adaptation of the selexipag dose is not required when co-administered with inhibitors of the organic anion-transporting polypeptide (OATP) 1B1/ 1B3, P-glycoprotein (P-gp) and/or CYP3A4. ..
  20. Noel Z, Kido K, Macaulay T. Selexipag for the treatment of pulmonary arterial hypertension. Am J Health Syst Pharm. 2017;74:1135-1141 pubmed publisher
    ..dosing and administration, and place in therapy of selexipag, an orally administered selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension (PAH), are reviewed...
  21. Lan N, Massam B, Kulkarni S, Lang C. Pulmonary Arterial Hypertension: Pathophysiology and Treatment. Diseases. 2018;6: pubmed publisher
    ..available: phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators, prostacyclin analogues, prostacyclin receptor agonists and endothelin receptor antagonists...
  22. Cutolo M, Ruaro B, Montagna P, Brizzolara R, Stratta E, Trombetta A, et al. Effects of selexipag and its active metabolite in contrasting the profibrotic myofibroblast activity in cultured scleroderma skin fibroblasts. Arthritis Res Ther. 2018;20:77 pubmed publisher
    ..Selexipag is a prostacyclin receptor agonist synthesized for the treatment of pulmonary arterial hypertension...
  23. Ng oma E, Groth M, Ripa R, Platzer M, Cellerino A. Transcriptome profiling of natural dichromatism in the annual fishes Nothobranchius furzeri and Nothobranchius kadleci. BMC Genomics. 2014;15:754 pubmed publisher
    ..However, an evolutionarily-conserved role of muscle-related genes in tail fin pigmentation is novel finding and interesting perspective for the future. ..
  24. Yang C, Demars K, Alexander J, Febo M, Candelario Jalil E. Sustained Neurological Recovery After Stroke in Aged Rats Treated With a Novel Prostacyclin Analog. Stroke. 2017;48:1948-1956 pubmed publisher
    ..5 hours after ischemia onset. Our data suggest that targeting the IP receptor with MRE-269 is a novel strategy to reduce cerebral ischemia injury and promote long-term neurological recovery in ischemic stroke. ..
  25. Laqqan M, Tierling S, Alkhaled Y, Lo Porto C, Solomayer E, Hammadeh M. Spermatozoa from males with reduced fecundity exhibit differential DNA methylation patterns. Andrology. 2017;5:971-978 pubmed publisher
    ..In addition, an association between changes in the methylation level for these CpGs and different semen parameters has been found. ..
  26. O Connell C, Amar D, Boucly A, Savale L, Jaïs X, Chaumais M, et al. Comparative Safety and Tolerability of Prostacyclins in Pulmonary Hypertension. Drug Saf. 2016;39:287-94 pubmed publisher
    ..Selexipag is the new oral non-prostanoid IP prostacyclin receptor agonist that has shown improved haemodynamics and good tolerance in a phase II study...
  27. Blitek A, Szymanska M, Morawska Pucinska E, Malysz Cymborska I, Andronowska A. Prostacyclin receptor (PTGIR) in the porcine endometrium: Regulation of expression and role in luminal epithelial and stromal cells. Theriogenology. 2015;84:969-82 pubmed publisher
    ..The present study was designed to examine (1) the expression of PGI2 receptor (PTGIR) messenger RNA (mRNA) and protein in the endometrium of cyclic and early-pregnant gilts; (2) possible ..
  28. Ghandour R, Giroud M, Vegiopoulos A, Herzig S, Ailhaud G, Amri E, et al. IP-receptor and PPARs trigger the conversion of human white to brite adipocyte induced by carbaprostacyclin. Biochim Biophys Acta. 2016;1861:285-93 pubmed publisher
    ..Thus dual pathways are playing in concert for the occurrence of a browning process of human white adipocytes. These results make prostacyclin analogs as a new class of interesting molecules to treat obesity and associated diseases. ..
  29. Fisch A, Tobusch K, Veit K, Meyer J, Darius H. Prostacyclin receptor desensitization is a reversible phenomenon in human platelets. Circulation. 1997;96:756-60 pubmed
    ..to endogenous or exogenous prostacyclin or its analogues might result in desensitization of the platelet prostacyclin receptor in vitro and in vivo accompanied by a loss in receptor density on the platelet surface and a reduced ..
  30. Ng H, Leo C, Parry L. Serelaxin (recombinant human relaxin-2) prevents high glucose-induced endothelial dysfunction by ameliorating prostacyclin production in the mouse aorta. Pharmacol Res. 2016;107:220-228 pubmed publisher
    ..Our data show that serelaxin treatment for 3 days restores high glucose-induced endothelial dysfunction by ameliorating vasodilator prostacyclin production and possibly through the reduction of superoxide in the mouse aorta. ..
  31. Chow K, Leung P, Cheng C, Cheung W, Wise H. The constitutive activity of ghrelin receptors is decreased by co-expression with vasoactive prostanoid receptors when over-expressed in human embryonic kidney 293 cells. Int J Biochem Cell Biol. 2008;40:2627-37 pubmed publisher
  32. Osawa T, Ohga N, Hida Y, Kitayama K, Akiyama K, Onodera Y, et al. Prostacyclin receptor in tumor endothelial cells promotes angiogenesis in an autocrine manner. Cancer Sci. 2012;103:1038-44 pubmed publisher
    ..Previously, using DNA microarray analysis, we found that the prostacyclin receptor (IP receptor) gene was upregulated in TEC compared with normal endothelial cells (NEC)...
  33. Wilson S, Roche A, Kostetskaia E, Smyth E. Dimerization of the human receptors for prostacyclin and thromboxane facilitates thromboxane receptor-mediated cAMP generation. J Biol Chem. 2004;279:53036-47 pubmed
    ..This represents a previously unknown mechanism by which IP may limit the cellular effects of TP. ..
  34. Fuchikami C, Murakami K, Tajima K, Homan J, Kosugi K, Kuramoto K, et al. A comparison of vasodilation mode among selexipag (NS-304; [2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide]), its active metabolite MRE-269 and various prostacyclin receptor agonists in rat, porcine and human pul. Eur J Pharmacol. 2017;795:75-83 pubmed publisher
    ..methylsulfonyl)acetamide]) is a novel, orally available non-prostanoid prostacyclin receptor (IP receptor) agonist that has recently been approved for the treatment of pulmonary arterial hypertension ..
  35. Boie Y, Rushmore T, Darmon Goodwin A, Grygorczyk R, Slipetz D, Metters K, et al. Cloning and expression of a cDNA for the human prostanoid IP receptor. J Biol Chem. 1994;269:12173-8 pubmed
    A cDNA clone coding for a functional human prostanoid IP receptor has been isolated from a lung cDNA library...
  36. Stockley J, Nisar S, Leo V, Sabi E, Cunningham M, Eikenboom J, et al. Identification and Characterization of Novel Variations in Platelet G-Protein Coupled Receptor (GPCR) Genes in Patients Historically Diagnosed with Type 1 von Willebrand Disease. PLoS ONE. 2015;10:e0143913 pubmed publisher
    ..The enrichment of single nucleotide variations in G protein-coupled receptor genes among type 1 von Willebrand disease patients supports the view of type 1 von Willebrand disease as a polygenic disorder. ..
  37. Hardin E, Chin K. Selexipag in the treatment of pulmonary arterial hypertension: design, development, and therapy. Drug Des Devel Ther. 2016;10:3747-3754 pubmed
    ..Selexipag, a novel, oral prostacyclin receptor agonist, has been shown to improve hemodynamics in a phase II clinical trial and reduce clinical worsening ..
  38. Li H, Hsu H, Chang G, Chen I, Ho W, Hsu P, et al. Prostanoid EP4 Agonist L-902,688 Activates PPAR? and Attenuates Pulmonary Arterial Hypertension. Am J Physiol Lung Cell Mol Physiol. 2017;:ajplung.00245.2017 pubmed publisher
    Prostacyclin agonists that bind the prostacyclin receptor (IP) to stimulate cyclic adenosine monophosphate (cAMP) synthesis are effective vasodilators for the treatment of idiopathic pulmonary arterial hypertension (IPAH) but this ..
  39. Lang I, Gaine S. Recent advances in targeting the prostacyclin pathway in pulmonary arterial hypertension. Eur Respir Rev. 2015;24:630-41 pubmed publisher
    ..pulmonary concentrations of prostacyclin, a prostanoid that targets several receptors including the IP prostacyclin receptor, are reduced...
  40. Morrison K, Haag F, Ernst R, Iglarz M, Clozel M. Selective Prostacyclin Receptor Agonist Selexipag, in Contrast to Prostacyclin Analogs, Does Not Evoke Paradoxical Vasoconstriction of the Rat Femoral Artery. J Pharmacol Exp Ther. 2018;365:727-733 pubmed publisher
    ..EP3 receptor-mediated vasoconstriction may contribute to the well documented peripheral muscle pain reported in patients with PAH receiving PGI2 analogs. Leg pain may be less in patients treated with selexipag. ..
  41. Tamura Y, Channick R. New paradigm for pulmonary arterial hypertension treatment. Curr Opin Pulm Med. 2016;22:429-33 pubmed publisher
    ..and GRIPHON evaluated the newer agents, macitentan, an endothelin receptor antagonist, and selexipag, a prostacyclin receptor agonist, respectively...
  42. Li Z, Zhang Y, Liu B, Luo W, Li H, Zhou Y. Role of E-type prostaglandin receptor EP3 in the vasoconstrictor activity evoked by prostacyclin in thromboxane-prostanoid receptor deficient mice. Sci Rep. 2017;7:42167 pubmed publisher
    ..I2 (PGI2), evokes contraction in vessels with limited expression of the prostacyclin receptor. Although the thromboxane-prostanoid receptor (TP) is proposed to mediate such a response of PGI2
  43. Badiani B, Messori A. Targeted Treatments for Pulmonary Arterial Hypertension: Interpreting Outcomes by Network Meta-analysis. Heart Lung Circ. 2016;25:46-52 pubmed publisher
    ..administered by oral, intravenous, subcutaneous or inhalatory route; 4) selective non-prostanoid prostacyclin receptor (IP receptor) agonists (sPRAs); 5) soluble guanylate cyclase stimulators (sGCSs)...
  44. Denton C, Hachulla E, Riemekasten G, Schwarting A, Frenoux J, Frey A, et al. Efficacy and Safety of Selexipag in Adults With Raynaud's Phenomenon Secondary to Systemic Sclerosis: A Randomized, Placebo-Controlled, Phase II Study. Arthritis Rheumatol. 2017;69:2370-2379 pubmed publisher
    To determine the effect of selexipag, an oral, selective IP prostacyclin receptor agonist, on the frequency of attacks of Raynaud's phenomenon (RP) in patients with systemic sclerosis (SSc).
  45. Bundey R, Insel P. Adenylyl cyclase 6 overexpression decreases the permeability of endothelial monolayers via preferential enhancement of prostacyclin receptor function. Mol Pharmacol. 2006;70:1700-7 pubmed
    ..adenoviral-mediated gene transfer of AC6 in human umbilical vein endothelial cells preferentially enhances prostacyclin receptor (versus other GPCR)-stimulated cAMP synthesis and, in parallel, inhibits thrombin-stimulated increases in ..
  46. Battersby S, Critchley H, de Brum Fernandes A, Jabbour H. Temporal expression and signalling of prostacyclin receptor in the human endometrium across the menstrual cycle. Reproduction. 2004;127:79-86 pubmed
    ..by investigating the temporal pattern and site of expression of prostaglandin I synthase (PGIS) and the prostacyclin receptor (IP receptor) in the non-pregnant human endometrium across the menstrual cycle...
  47. Mous D, Buscop van Kempen M, Wijnen R, Tibboel D, Rottier R. Changes in vasoactive pathways in congenital diaphragmatic hernia associated pulmonary hypertension explain unresponsiveness to pharmacotherapy. Respir Res. 2017;18:187 pubmed publisher
    ..This knowledge could have important implications for the choice of drugs and the design of future clinical trials internationally. ..
  48. Zhang L, Huang G, Wu J, Ruan K. A profile of the residues in the first intracellular loop critical for Gs-mediated signaling of human prostacyclin receptor characterized by an integrative approach of NMR-experiment and mutagenesis. Biochemistry. 2005;44:11389-401 pubmed
    The first intracellular loop (iLP1, residues 39-51) of human prostacyclin receptor (IP) was proposed to be involved in signaling via its interaction with the Galphas protein...
  49. Eivers S, Kinsella B. Regulated expression of the prostacyclin receptor (IP) gene by androgens within the vasculature: Combined role for androgens and serum cholesterol. Biochim Biophys Acta. 2016;1859:1333-51 pubmed publisher
    ..This may explain, in part, some of the protective actions of androgens within the vasculature. ..
  50. Grilo A, Sáez Rosas M, Santos Morano J, Sanchez E, Moreno Rey C, Real L, et al. Identification of genetic factors associated with susceptibility to angiotensin-converting enzyme inhibitors-induced cough. Pharmacogenet Genomics. 2011;21:10-7 pubmed publisher
    ..384 for protective combinations and 2.732?OR?7.216 for risk combinations). These results are consistent with the hypothesis that the mechanism of cough is related to the accumulation of bradykinin, substance P, and prostaglandins. ..
  51. Hoeper M, McLaughlin V, Dalaan A, Satoh T, Galiè N. Treatment of pulmonary hypertension. Lancet Respir Med. 2016;4:323-36 pubmed publisher
    ..phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators, prostacyclin analogues, and prostacyclin receptor agonists...
  52. Kim S, Kim Y, Park H, Jee Y, Kim S, Bahn J, et al. Association between polymorphisms in prostanoid receptor genes and aspirin-intolerant asthma. Pharmacogenet Genomics. 2007;17:295-304 pubmed
    ..015). These findings suggest that genetic polymorphisms in PTGER2, PTGER3, PTGER4, PTGIR, and TBXA2R play important roles in the pathogenesis of aspirin-intolerant asthma. ..
  53. Fortier I, Patry C, Lora M, Samadfan R, de Brum Fernandes A. Immunohistochemical localization of the prostacyclin receptor (IP) human bone. Prostaglandins Leukot Essent Fatty Acids. 2001;65:79-83 pubmed
  54. He T, Santhanam A, Lu T, d Uscio L, Katusic Z. Role of prostacyclin signaling in endothelial production of soluble amyloid precursor protein-α in cerebral microvessels. J Cereb Blood Flow Metab. 2017;37:106-122 pubmed
    ..Our findings identified previously unrecognized role of IP-PPARδ signal transduction pathway in the production of sAPPα in cerebral microvasculature. ..
  55. Smyth E, Fitzgerald G. Human prostacyclin receptor. Vitam Horm. 2002;65:149-65 pubmed
    ..This article examines the current state of knowledge of the IP, its signaling and regulation, and its biological role in vivo and examines the possible existence of multiple PGI2 receptor sites.
  56. Kheirollahi M, Pourreza M, Khorvash F, Kazemi M, Amini G. A Report of a Novel Mutation in Human Prostacyclin Receptor Gene in Patients Affected with Migraine. Iran J Psychiatry. 2017;12:219-222 pubmed
    b>Objective: The human prostacyclin receptor gene encodes the human prostacyclin receptor, which is a part of the vasodilator system, during migraine attacks and almost certainly plays an important role in the mechanism of this ..
  57. Lo R, Wise H, Wong Y. Prostacyclin receptor induces STAT1 and STAT3 phosphorylations in human erythroleukemia cells: a mechanism requiring PTX-insensitive G proteins, ERK and JNK. Cell Signal. 2006;18:307-17 pubmed
    The ability of the human prostacyclin receptor (hIP) to regulate the activities of signal transducers and activators of transcription (STATs) has not yet been documented...
  58. Lau A, Lai H, Yeung B, Leung S, Tsang S, Wong Y, et al. Prostacyclin receptor-dependent inhibition of human erythroleukemia cell differentiation is STAT3-dependent. Prostaglandins Leukot Essent Fatty Acids. 2012;86:119-26 pubmed publisher
  59. Jasińska Stroschein M, Orszulak Michalak D. Novel strategies for treatment of pulmonary arterial hypertension. Postepy Hig Med Dosw (Online). 2017;71:577-588 pubmed
    ..We focused on novel molecular mechanisms in PAH of recently approved: Guanylate cyclase stimulator and non-prostanoid IP receptor agonist...
  60. Fetalvero K, Shyu M, Nomikos A, Chiu Y, Wagner R, Powell R, et al. The prostacyclin receptor induces human vascular smooth muscle cell differentiation via the protein kinase A pathway. Am J Physiol Heart Circ Physiol. 2006;290:H1337-46 pubmed
    ..This provides important mechanistic insights into the induction of cardiovascular events with the use of selective COX-2 inhibitors. ..
  61. Falcetti E, Hall S, Phillips P, Patel J, Morrell N, Haworth S, et al. Smooth muscle proliferation and role of the prostacyclin (IP) receptor in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med. 2010;182:1161-70 pubmed publisher
    ..PPAR? may represent a previously unrecognized pathway by which these agents inhibit smooth muscle proliferation. ..
  62. Rauvala H, Peng H. HB-GAM (heparin-binding growth-associated molecule) and heparin-type glycans in the development and plasticity of neuron-target contacts. Prog Neurobiol. 1997;52:127-44 pubmed
    ..In addition, a role in adult plasticity is suggested by studies on injury-induced and activity-dependent plasticity in rat hippocampus. ..
  63. Frey A, Ibrahim S, Gleim S, Hwa J, Smyth E. Biased suppression of TP homodimerization and signaling through disruption of a TM GxxxGxxxL helical interaction motif. J Lipid Res. 2013;54:1678-90 pubmed publisher
    ..Heterodimerization of TP? with the functionally opposing prostacyclin receptor (IP) shifts TP? to signal via the IP-Gs cascade contributing to prostacyclin's restraint of TXA2 function...
  64. Ibrahim S, McCartney A, Markosyan N, Smyth E. Heterodimerization with the prostacyclin receptor triggers thromboxane receptor relocation to lipid rafts. Arterioscler Thromb Vasc Biol. 2013;33:60-6 pubmed publisher
    ..We speculate that changes in IP and IPTP signaling after perturbation of membrane cholesterol may contribute to cardiovascular disease associated with hypercholesterolemia. ..
  65. Wieland T, Michel M. Can a GDP-liganded G-protein be active?. Mol Pharmacol. 2005;68:559-62 pubmed
    ..We summarize here the evidence that GTP is necessary for effector activation by G-proteins and discuss potential implications and limitations of data to the contrary. ..
  66. Li R, Grosser T, Diamond S. Microfluidic whole blood testing of platelet response to pharmacological agents. Platelets. 2017;28:457-462 pubmed publisher
    ..platelet deposition under flow, as do NO donors and iloprost that target the guanylate cyclase and the prostacyclin receptor, respectively...
  67. Ni F, So S, Cervantes V, Ruan K. A profile of the residues in the second extracellular loop that are critical for ligand recognition of human prostacyclin receptor. FEBS J. 2008;275:128-37 pubmed
    ..To further test this hypothesis, another prostanoid receptor, the prostacyclin receptor (IP), which has opposite biological characteristics to that of TP, was used as a model for these studies...
  68. Kahn N, Bauman W, Sinha A. Circulating heavy chain IgG, a pathological mediator for coronary artery disease, recognizes platelet surface receptors of both prostacyclin and insulin. Platelets. 2003;14:203-10 pubmed
    ..of the hormone binding, Kd1 = 2 x 10(-9) M) for the synthesis of nitric oxide but also blocked the prostacyclin receptor interaction in normal platelets...
  69. Ogawa Y, Tanaka I, Inoue M, Yoshitake Y, Isse N, Nakagawa O, et al. Structural organization and chromosomal assignment of the human prostacyclin receptor gene. Genomics. 1995;27:142-8 pubmed
    b>Prostacyclin receptor is a member of the prostanoid receptor family in the G protein-coupled receptor superfamily with seven transmembrane domains...
  70. Mulvaney E, O Meara F, Khan A, O Connell D, Kinsella B. Identification of ?-helix 4 (?4) of Rab11a as a novel Rab11-binding domain (RBD): Interaction of Rab11a with the Prostacyclin Receptor. Biochim Biophys Acta Mol Cell Res. 2017;1864:1819-1832 pubmed publisher
    ..In the case of the human prostacyclin receptor (hIP), it undergoes agonist-induced internalization and subsequent Rab11a-dependent recyclization ..
  71. Zhang L, Bastepe M, Juppner H, Ruan K. Characterization of the molecular mechanisms of the coupling between intracellular loops of prostacyclin receptor with the C-terminal domain of the Galphas protein in human coronary artery smooth muscle cells. Arch Biochem Biophys. 2006;454:80-8 pubmed
    ..C-terminal domain of the Gs protein alpha subunit (Galphas Ct) and the first intracellular loop (iLP1) of prostacyclin receptor (IP) have been predicted to be involved in the receptor signaling mediated through the IP/Gs protein ..
  72. Zhang L, Wu J, Ruan K. Solution structure of the first intracellular loop of prostacyclin receptor and implication of its interaction with the C-terminal segment of G alpha s protein. Biochemistry. 2006;45:1734-44 pubmed
    ..residues 39-51) responsible for the interaction between the first intracellular loop (iLP1) of the human prostacyclin receptor (IP) and G alpha s protein have been identified [Zhang, L., Huang, G., Wu, J., and Ruan, K. H...
  73. Colombe L, Michelet J, Bernard B. Prostanoid receptors in anagen human hair follicles. Exp Dermatol. 2008;17:63-72 pubmed
    ..Although extracting a clear functional significance from this intricate network remains open challenge, FP labelling, i.e. could explain the biological effect of PGF(2alpha) on hair regrowth, by directly modulating DP function. ..
  74. Duncan A, Anderson L, Funk C, Abramovitz M, Adam M. Chromosomal localization of the human prostanoid receptor gene family. Genomics. 1995;25:740-2 pubmed
    ..that encode the PGE2 receptor subtypes (PTGER1, PTGER2, and PTGER3), the PGF2 alpha receptor (PTGFR), the PGI2 receptor (PTGIR), and the TXA2 receptor (TBXA2R) using in situ hybridization...
  75. Coleman R, Smith W, Narumiya S. International Union of Pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes. Pharmacol Rev. 1994;46:205-29 pubmed
  76. Khan F, Syeda P, Nartey M, Rahman M, Islam M, Nishimura K, et al. Stimulation of fat storage by prostacyclin and selective agonists of prostanoid IP receptor during the maturation phase of cultured adipocytes. Cytotechnology. 2016;68:2417-2429 pubmed
    ..during the maturation phase by the positive regulation of gene expression of PGI synthase and the prostanoid IP receptor. To clarify how prostacyclin regulates adipogenesis, we investigated the effects of prostacyclin and the ..
  77. Batchu S, Majumder S, Bowskill B, White K, Advani S, Brijmohan A, et al. Prostaglandin I2 Receptor Agonism Preserves β-Cell Function and Attenuates Albuminuria Through Nephrin-Dependent Mechanisms. Diabetes. 2016;65:1398-409 pubmed publisher
    ..Collectively, these observations describe a pharmacological strategy that posttranslationally modifies nephrin and the effects of this strategy in the pancreas and in the kidney. ..
  78. Plum J, Huang C, Grabensee B, Schror K, Meyer Kirchrath J. Prostacyclin enhances the expression of LPS/INF-gamma-induced nitric oxide synthase in human monocytes. Nephron. 2002;91:391-8 pubmed
    ..This study was designed to investigate the influence of prostacyclin receptor (IP receptor) activation on iNOS expression and NO formation in human peripheral blood monocytes...
  79. Sasaki Y, Takahashi T, Tanaka I, Nakamura K, Okuno Y, Nakagawa O, et al. Expression of prostacyclin receptor in human megakaryocytes. Blood. 1997;90:1039-46 pubmed
    ..Also, it was indicated that megakaryocytic maturation accompanies enhancement of PGI2-R expression. ..
  80. Muto A, Nishibe T, Miyauchi Y, Kondo Y, Yamamoto Y, Dardik A, et al. Prostaglandin receptors EP2 and IP are detectable in atherosclerotic arteries and plaques. Int Angiol. 2010;29:43-8 pubmed
    ..These results suggest that receptor-selective PG agonists specifically target atherosclerotic arteries and therefore, may find potential application in the pharmacological management of patients with ASO. ..
  81. Kömhoff M, Lesener B, Nakao K, Seyberth H, Nüsing R. Localization of the prostacyclin receptor in human kidney. Kidney Int. 1998;54:1899-908 pubmed
    ..into the network of prostacyclin signal transduction, we analyzed the intrarenal distribution of the prostacyclin receptor (IP receptor) in adult human kidney...
  82. Nobles M, Benians A, Tinker A. Heterotrimeric G proteins precouple with G protein-coupled receptors in living cells. Proc Natl Acad Sci U S A. 2005;102:18706-11 pubmed
    ..In contrast, the predominantly Gs-coupled prostacyclin receptor interacted with Gs, but there was little interaction between the prostacyclin receptor and Go...
  83. Liu W, Li H, Zhang X, Wen D, Yu F, Yang S, et al. Prostaglandin I2-IP signalling regulates human Th17 and Treg cell differentiation. Prostaglandins Leukot Essent Fatty Acids. 2013;89:335-44 pubmed publisher
    ..Together with previous results, these data suggest that prostanoids play an important role in the pathogenesis of autoimmune diseases, such as rheumatoid arthritis. ..
  84. Donnellan P, Kimbembe C, Reid H, Kinsella B. Identification of a novel endoplasmic reticulum export motif within the eighth ?-helical domain (?-H8) of the human prostacyclin receptor. Biochim Biophys Acta. 2011;1808:1202-18 pubmed publisher
    The human prostacyclin receptor (hIP) undergoes agonist-dependent trafficking involving a direct interaction with Rab11a GTPase...