pituitary hormone receptors

Summary

Summary: Cell surface proteins that bind pituitary hormones with high affinity and trigger intracellular changes influencing the behavior of cells. Since many pituitary hormones are also released by neurons as neurotransmitters, these receptors are also found in the nervous system.

Top Publications

  1. Campbell B, Dickey J, Beckman B, Young G, Pierce A, Fukada H, et al. Previtellogenic oocyte growth in salmon: relationships among body growth, plasma insulin-like growth factor-1, estradiol-17beta, follicle-stimulating hormone and expression of ovarian genes for insulin-like growth factors, steroidogenic-acute regulat. Biol Reprod. 2006;75:34-44 pubmed
  2. Fukamachi S, Yada T, Mitani H. Medaka receptors for somatolactin and growth hormone: phylogenetic paradox among fish growth hormone receptors. Genetics. 2005;171:1875-83 pubmed publisher
    ..These results may indicate lineage-specific diversification of SLR and GHR functions among fish or just an inappropriate naming of these receptors. Further functional and comparative reassessments are necessary to address this question...
  3. Zhang Q, Yuan C, Wu M, Wang Y, Qin Q, Shi Y, et al. Comparative proteomic analysis of proteins influenced by melanin-concentrating hormone and melanin-concentrating hormone receptor 2 interaction. Horm Metab Res. 2010;42:521-7 pubmed publisher
    ..The comparative proteome data may provide a valuable clue to further understand MCHR2 physiological function, and several differentially regulated proteins may be used as target proteins for the development of novel drugs. ..
  4. Persson K, Ahren B. The neuropeptide PACAP contributes to the glucagon response to insulin-induced hypoglycaemia in mice. Acta Physiol Scand. 2002;175:25-8 pubmed
    ..Therefore, the glucagon response to hypoglycaemia is dependent not only on the classical neurotransmitters but also on the neuropeptide PACAP. ..
  5. Thomson F, Craighead M. Innovative approaches for the treatment of depression: targeting the HPA axis. Neurochem Res. 2008;33:691-707 pubmed
    ..Agents that intervene with the mechanisms involved in (dys)regulation of cortisol synthesis and release are under investigation as possible therapeutic agents. The current status of some of these approaches is described in this review. ..
  6. Isobe K, Tatsuno I, Yashiro T, Nanmoku T, Takekoshi K, Kawakami Y, et al. Expression of mRNA for PACAP and its receptors in intra- and extra-adrenal human pheochromocytomas and their relationship to catecholamine synthesis. Regul Pept. 2003;110:213-7 pubmed
    ..0342) levels in 16 intra-adrenal pheochromocytomas. Our findings support a possible role for PACAP in the regulation of expression of genes encoding catecholamine-synthesizing enzymes in intra-adrenal pheochromocytomas. ..
  7. Bednarek M, Tan C, Hreniuk D, Palyha O, MacNeil D, Van Der Ploeg L, et al. Synthesis and biological evaluation in vitro of a selective, high potency peptide agonist of human melanin-concentrating hormone action at human melanin-concentrating hormone receptor 1. J Biol Chem. 2002;277:13821-6 pubmed
    ..Apparently, these structural changes in positions 6 and 10 results in peptide conformations that allow for efficient interactions with hMCH-1R but are unfavorable for molecular recognition at hMCH-2R. ..
  8. Läuffer J, Tang L, Zhang T, Hinoue T, Rahbar S, Odo M, et al. PACAP mediates the neural proliferative pathway of Mastomys enterochromaffin-like cell transformation. Regul Pept. 2001;102:157-64 pubmed
    ..The expression of this neuropeptide and its receptors, particularly PAC1, suggest the existence of a neural regulatory pathway of ECL cell proliferation and transformation. ..
  9. Aubert M, Rivest R, Lang U, Winiger B, Sizonenko P. Delayed sexual maturation induced by daily melatonin administration eliminates the LH response to naloxone despite normal responsiveness to GnRH in juvenile male rats. Neuroendocrinology. 1988;48:72-80 pubmed
    ..0 mg/kg, s.c.) prevented the NAL-induced rise of plasma LH in control rats at day 40 of life. In all instances, plasma PRL levels were decreased after NAL both in untreated and in MT-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS) ..

More Information

Publications62

  1. Koh P, Kwak S, Kim H, Roh G, Kim J, Kang S, et al. Expression patterns of pituitary adenylate cyclase activating polypeptide and its type I receptor mRNAs in the rat placenta. Mol Reprod Dev. 2003;64:27-31 pubmed
  2. Verlaet M, Adamantidis A, Coumans B, Chanas G, Zorzi W, Heinen E, et al. Human immune cells express ppMCH mRNA and functional MCHR1 receptor. FEBS Lett. 2002;527:205-10 pubmed
    ..Moreover, MCH treatment decreases the CD3-stimulated PBMC proliferation in vitro. Accordingly, our data indicate for the first time that MCH and MCHR1 may exert immunomodulatory functions. ..
  3. Hoogduijn M, Ancans J, Suzuki I, Estdale S, Thody A. Melanin-concentrating hormone and its receptor are expressed and functional in human skin. Biochem Biophys Res Commun. 2002;296:698-701 pubmed
    ..Furthermore, the melanogenic actions of alpha-MSH were inhibited by MCH. We propose that the MCH/MCHR1 signalling system is present in human skin and may have a role with the melanocortins in regulating the melanocyte. ..
  4. Kemp E, Waterman E, Hawes B, O Neill K, Gottumukkala R, Gawkrodger D, et al. The melanin-concentrating hormone receptor 1, a novel target of autoantibody responses in vitiligo. J Clin Invest. 2002;109:923-30 pubmed
    ..Inhibition of MCH binding to its receptor by IgG from vitiligo patients was also shown. ..
  5. Grimaldi M, Cavallaro S. Functional and molecular diversity of PACAP/VIP receptors in cortical neurons and type I astrocytes. Eur J Neurosci. 1999;11:2767-72 pubmed
  6. Svoboda M, Tastenoy M, Ciccarelli E, Stievenart M, Christophe J. Cloning of a splice variant of the pituitary adenylate cyclase-activating polypeptide (PACAP) type I receptor. Biochem Biophys Res Commun. 1993;195:881-8 pubmed
    ..This indicated that common alternative splicing provokes the diversification of PACAP type I receptors into PACAPR1A (unspliced) and PACAPR1B (spliced) variants. ..
  7. Kirchgessner A, Liu M. Pituitary adenylate cyclase activating peptide (PACAP) in the enteropancreatic innervation. Anat Rec. 2001;262:91-100 pubmed
    ..These results provide support for the hypothesis that PACAP modulates reflex activity between the gut and pancreas. The excitatory effect of PACAP would be expected to potentiate pancreatic secretion. ..
  8. Derand R, Montoni A, Bulteau Pignoux L, Janet T, Moreau B, Muller J, et al. Activation of VPAC1 receptors by VIP and PACAP-27 in human bronchial epithelial cells induces CFTR-dependent chloride secretion. Br J Pharmacol. 2004;141:698-708 pubmed
    ..7. This study shows the stimulation in human bronchial epithelial cells of CFTR-dependent chloride secretion following activation by VIP and PACAP-27 of basolateral VPAC(1) receptors. ..
  9. Luscombe C, French M, Liu S, Saxby M, Jones P, Fryer A, et al. Outcome in prostate cancer associations with skin type and polymorphism in pigmentation-related genes. Carcinogenesis. 2001;22:1343-7 pubmed
    ..040, OR 0.41) or approached significance (P = 0.052, OR 0.44), respectively. These data indicate for the first time that pigmentation response to UV is associated with outcome in prostate cancer. ..
  10. Schlumberger S, Saito Y, Giller T, Hintermann E, Tanner H, Jäggin V, et al. Different structural requirements for melanin-concentrating hormone (MCH) interacting with rat MCH-R1 (SLC-1) and mouse B16 cell MCH-R. J Recept Signal Transduct Res. 2003;23:69-81 pubmed
    ..These data demonstrate that ligand recognition by B16 MCH-R differs from that of MCH-R1 in several respects, indicating that the B16 MCH-R represents an MCH-R subtype different from MCH-R1. ..
  11. Kato J, Uddman R, Sundler F, Kurisu K. Immunohistochemical study of the innervation of the boundary area of the hard and soft palates of the rat. Acta Anat (Basel). 1998;163:92-8 pubmed
    ..Many of the VIP- and c-PON-containing nerve fibers were associated with blood vessels. In addition, nerve fibers containing PGP 9.5, CGRP, SP and c-PON were observed around, and penetrating into, the taste buds in the boundary area. ..
  12. Miampamba M, Germano P, Arli S, Wong H, Scott D, TACHE Y, et al. Expression of pituitary adenylate cyclase-activating polypeptide and PACAP type 1 receptor in the rat gastric and colonic myenteric neurons. Regul Pept. 2002;105:145-54 pubmed
    ..5 (PGP 9.5) revealed the neuronal identity of myenteric cells bearing PAC1. The neuronal localization of PACAP and PAC1 receptors supports their role in the neural regulation of gastric acid secretion and gastrointestinal motor function. ..
  13. Morrow J, Lutz E, West K, Fink G, Harmar A. Molecular cloning and expression of a cDNA encoding a receptor for pituitary adenylate cyclase activating polypeptide (PACAP). FEBS Lett. 1993;329:99-105 pubmed
    ..The order of potency of these ligands was PACAP-38-PACAP-27 > VIP > PHI, suggesting that the receptor corresponds to the pharmacologically characterised PACAP Type I receptor. ..
  14. Shearman L, Camacho R, Sloan Stribling D, Zhou D, Bednarek M, Hreniuk D, et al. Chronic MCH-1 receptor modulation alters appetite, body weight and adiposity in rats. Eur J Pharmacol. 2003;475:37-47 pubmed
    ..001), body weight gain (-35%, P<0.01), and body fat gain relative to controls, without an effect on lean mass. Antagonism of the MCH-1 receptor may be an effective approach for the treatment of obesity. ..
  15. Yamaguchi N, Minassian T, Yamaguchi S. Effects of PACAP(1-27) on the canine endocrine pancreas in vivo: interaction with cholinergic mechanism. Can J Physiol Pharmacol. 2003;81:720-9 pubmed
  16. Kimura H, Kawatani M, Ito E, Ishikawa K. Effects of pituitary adenylate cyclase-activating polypeptide on facial nerve recovery in the Guinea pig. Laryngoscope. 2003;113:1000-6 pubmed
    ..Pituitary adenylate cyclase-activating polypeptide prolonged the GDNF levels in target organs. These data indicated that PACAP promoted regeneration of the facial nerve. ..
  17. Takeuchi S, Suzuki S, Hirose S, Yabuuchi M, Sato C, Yamamoto H, et al. Molecular cloning and sequence analysis of the chick melanocortin 1-receptor gene. Biochim Biophys Acta. 1996;1306:122-6 pubmed
    ..A cis-element responsible for melanocyte-specific transcription is found in its 5' upstream region. It is probable that the expression of the receptor in melanocytes is closely correlated with that of melanogenesis-related genes. ..
  18. Valverde P, Healy E, Sikkink S, Haldane F, Thody A, Carothers A, et al. The Asp84Glu variant of the melanocortin 1 receptor (MC1R) is associated with melanoma. Hum Mol Genet. 1996;5:1663-6 pubmed
    ..The contribution of variant MC1R alleles was largely independent of skin type. Variants of the MC1R gene are likely to be causally associated with the development of melanoma. ..
  19. Tatman W, Judkins M, Dunn T, Moss G. Luteinizing hormone in nutrient-restricted ovariectomized ewes. J Anim Sci. 1990;68:1097-102 pubmed
    ..01) in ewes with CS less than or equal to 2 compared with ewes with CS greater than or equal to 3 (2.6 vs 9.5 and 3.2 vs 10.5 ng/ml for basal and mean concentrations, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) ..
  20. Nachman R, Ben Aziz O, Davidovitch M, Kaczmarek K, Zabrocki J, Williams H, et al. A novel dihydroimidazoline, trans-Pro mimetic analog is a selective PK/PBAN agonist. Front Biosci (Elite Ed). 2010;2:195-203 pubmed
  21. Kym P, Judd A, Lynch J, Iyengar R, Vasudevan A, Souers A. Lead optimization strategies and tactics applied to the discovery of melanin concentrating hormone receptor 1 antagonists. Curr Top Med Chem. 2007;7:1471-88 pubmed
  22. Nowak J, Zawilska J. PACAP in avians: origin, occurrence, and receptors--pharmacological and functional considerations. Curr Pharm Des. 2003;9:467-81 pubmed
  23. Siebel A, Bathgate R, Parry L. Differential expression of mesotocin receptors in the uterus and ovary of the pregnant tammar wallaby. Reproduction. 2005;129:639-49 pubmed
    ..The pattern of luteal mesotocin receptor expression differed from the myometrium, with a decrease in mesotocin receptors occurring on the day of expected births. ..
  24. Pisegna J, Lyu R, Germano P. Essential structural motif in the C-terminus of the PACAP type I receptor for signal transduction and internalization. Ann N Y Acad Sci. 2000;921:195-201 pubmed
    ..These results indicate that a structural motif within the proximal region of the carboxyl terminus is critical for G protein coupling. ..
  25. Montpetit C, Shahsavarani A, Perry S. Localisation of VIP-binding sites exhibiting properties of VPAC receptors in chromaffin cells of rainbow trout (Oncorhynchus mykiss). J Exp Biol. 2003;206:1917-27 pubmed
    ..However, the selective secretion of adrenaline by VIP or PACAP cannot be explained by a lack of VIP-binding sites on the noradrenaline-containing cells. ..
  26. Griffond B, Baker B. Cell and molecular cell biology of melanin-concentrating hormone. Int Rev Cytol. 2002;213:233-77 pubmed
    ..Evidence that MCH also has peripheral paracrine/autocrine effects in mammals is provided. ..
  27. McBriar M. Melanin concentrating hormone receptor antagonists as antiobesity agents: from M2 to MCHR-1. Curr Top Med Chem. 2007;7:1440-54 pubmed
    ..Several challenges such as selectivity over other receptors, toxicity of a potential metabolite and determining receptor occupancy via a medium throughput assay will be reviewed. ..
  28. Yon L, Chartrel N, Feuilloley M, De Marchis S, Fournier A, De Rijk E, et al. Pituitary adenylate cyclase-activating polypeptide stimulates both adrenocortical cells and chromaffin cells in the frog adrenal gland. Endocrinology. 1994;135:2749-58 pubmed
    ..PACAP also increases intracellular Ca2+ in chromaffin cells. These data suggest that PACAP, released locally in the adrenal gland, acts as a neuroendocrine factor, regulating the activity of adrenocortical and chromaffin cells...
  29. Ichinose M, Asai M, Sawada M. Activation of outward current by pituitary adenylate cyclase activating polypeptide in mouse microglial cells. J Neurosci Res. 1998;51:382-90 pubmed
    ..These data suggest that PACAP38 activates a quinine-sensitive K+ outward current and modulates activities in microglia. They indicate that the immune system in the brain can be modulated by neurotransmitters, the mediators of neurons. ..
  30. Shinohara K, Funabashi T, Nakamura T, Mitsushima D, Kimura F. Differential regulation of pituitary adenylate cyclase-activating peptide receptor variants in the rat suprachiasmatic nucleus. Neuroscience. 2002;110:301-8 pubmed
    ..These results suggest that PAC(1) splice variants are differentially regulated in the rat suprachiasmatic nucleus. ..
  31. Rowbottom M, Vickers T, Tamiya J, Zhang M, Dyck B, Grey J, et al. Synthesis and structure-activity relationships of spirohydantoin-derived small-molecule antagonists of the melanin-concentrating hormone receptor-1 (MCH-R1). Bioorg Med Chem Lett. 2007;17:2171-8 pubmed
    ..The design, synthesis, and SAR of a series of substituted spirohydantoins are described. Optimization of an in-house screening hit gave compounds that exhibited potent binding affinity and functional activity at MCH-R1. ..
  32. Bednarek M, Silva M, Arison B, MacNeil T, Kalyani R, Huang R, et al. Structure-function studies on the cyclic peptide MT-II, lactam derivative of alpha-melanotropin. Peptides. 1999;20:401-9 pubmed
    ..The nuclear magnetic resonance analysis of MT-II suggested involvement of Phe and Arg residues in H-bonds stabilizing the bent conformations of the peptide backbone. ..
  33. Oh K, Ryu S, Lee S, Seo H, Oh B, Kim Y, et al. Melanin-concentrating hormone-1 receptor antagonism and anti-obesity effects of ethanolic extract from Morus alba leaves in diet-induced obese mice. J Ethnopharmacol. 2009;122:216-20 pubmed
    ..These results suggest that chronic treatment with EMA exerts an anti-obesity effect in DIO mice, and its direct MCH1 receptor antagonism may contribute to decrease body weight. ..
  34. Berglund S, Egner B, Gradén H, Gradén J, Morgan D, Inghardt T, et al. Optimization of piperidin-4-yl-urea-containing melanin-concentrating hormone receptor 1 (MCH-R1) antagonists: Reducing hERG-associated liabilities. Bioorg Med Chem Lett. 2009;19:4274-9 pubmed publisher
    ..Different strategies to increase hERG selectivity were implemented and resulted in the identification of piperidin-4-yl-urea compounds as potent MCH-R1 antagonists with minimized hERG inhibition. ..
  35. Oh B, Oh K, Kwon K, Ryu S, Kim Y, Lee B. Melanin-concentrating hormone-1 receptor binding activity of pheophorbides isolated from Morus alba leaves. Phytother Res. 2010;24:919-23 pubmed publisher
    ..These results suggest that pheophorbide a methyl ester and 13(2)(S)-hydroxypheophorbide a methyl ester act as modulators of MCH-1 receptor and MCH-mediated ERK signaling. ..
  36. Hertzog D, Witty D. Biphenyl amides and isosteres as MCH R1 antagonists. Curr Top Med Chem. 2007;7:1455-70 pubmed
    ..Importantly, these MCH R1 antagonists have demonstrated efficacy in animal models of obesity through once-daily oral administration at low doses. ..
  37. Everts R, Rothuizen J, van Oost B. Identification of a premature stop codon in the melanocyte-stimulating hormone receptor gene (MC1R) in Labrador and Golden retrievers with yellow coat colour. Anim Genet. 2000;31:194-9 pubmed
    ..Seventeen other breeds were all negative for the mutation. Since the Labrador and Golden retriever are closely related, we suggest a common founder for the yellow coat colour in Labrador and Golden retrievers. ..
  38. Saito Y, Wang Z, Hagino Yamagishi K, Civelli O, Kawashima S, Maruyama K. Endogenous melanin-concentrating hormone receptor SLC-1 in human melanoma SK-MEL-37 cells. Biochem Biophys Res Commun. 2001;289:44-50 pubmed
    ..This study provides for the first time a skin-derived cellular model to analyze the molecular mechanism of the MCH signaling pathway. ..
  39. Murakami Y, Koshimura K, Yamauchi K, Nishiki M, Tanaka J, Kato Y. Roles and mechanisms of action of pituitary adenylate cyclase-activating polypeptide (PACAP) in growth hormone and prolactin secretion. Endocr J. 2001;48:123-32 pubmed
    ..PACAP can stimulate PRL release from the pituitary in rats possibly through indirect paracrine effect. In addition, PACAP might participate in regulation of PRL secretion via hypothalamic VIP. ..
  40. Mori M, Harada M, Terao Y, Sugo T, Watanabe T, Shimomura Y, et al. Cloning of a novel G protein-coupled receptor, SLT, a subtype of the melanin-concentrating hormone receptor. Biochem Biophys Res Commun. 2001;283:1013-8 pubmed
    ..The distribution of the SLT nearly overlapped that of SLC-1, suggesting that some of the neural functions of MCH may be mediated by both of these receptor subtypes. ..
  41. Cameron J. Interrelationships between hormones, behavior, and affect during adolescence: understanding hormonal, physical, and brain changes occurring in association with pubertal activation of the reproductive axis. Introduction to part III. Ann N Y Acad Sci. 2004;1021:110-23 pubmed
  42. Zawilska J, Niewiadomski P, Nowak J. PAC1 receptors in chick cerebral cortex: characterization by binding of pituitary adenylate cyclase-activating polypeptide, [125I]-PACAP27. Neurosci Lett. 2003;338:155-8 pubmed
    ..It is concluded that the cerebral cortex of chick, in addition to VPAC recognition sites, contains a large population of PAC(1)-type receptor binding sites. ..
  43. Gillardon F, Hata R, Hossmann K. Delayed up-regulation of Zac1 and PACAP type I receptor after transient focal cerebral ischemia in mice. Brain Res Mol Brain Res. 1998;61:207-10 pubmed
    ..Late induction of cell death promoting Zac1 in the post-ischemic brain may be attributed to delayed or secondary cell death. Co-induction of the type I receptor for neurotrophic PACAP however, points to a role in restorative processes. ..
  44. Inooka H, Ohtaki T, Kitahara O, Ikegami T, Endo S, Kitada C, et al. Conformation of a peptide ligand bound to its G-protein coupled receptor. Nat Struct Biol. 2001;8:161-5 pubmed
  45. Morales Bayuelo A, Ayazo H, Vivas Reyes R. Three-dimensional quantitative structure-activity relationship CoMSIA/CoMFA and LeapFrog studies on novel series of bicyclo [4.1.0] heptanes derivatives as melanin-concentrating hormone receptor R1 antagonists. Eur J Med Chem. 2010;45:4509-22 pubmed publisher
    ..1.0] heptanes, using the model CoMFA which also was used for the molecular design using the technique LeapFrog. The data generated from the present study will further help to design novel, potent, and selective MCHR1 antagonists. ..
  46. Kawauchi H, Baker B. Melanin-concentrating hormone signaling systems in fish. Peptides. 2004;25:1577-84 pubmed
    ..The aim of this article is to review the recent data on MCH and MCH receptor signaling systems in fish. ..
  47. Clark A, McLoughlin L, Grossman A. Familial glucocorticoid deficiency associated with point mutation in the adrenocorticotropin receptor. Lancet. 1993;341:461-2 pubmed
    ..This is only the second clinical disorder associated with a GTP-binding-protein-linked hormone-receptor mutation. ..
  48. Yada T, Sakurada M, Nakata M, Ihida K, Yaekura K, Shioda S, et al. Current status of PACAP as a regulator of insulin secretion in pancreatic islets. Ann N Y Acad Sci. 1996;805:329-40; discussion 341-2 pubmed
    ..Finally, we hypothesize that PACAP is a pancreatic peptide of both neural and islet origin and functions as an intrinsic potentiator of glucose-induced insulin secretion in pancreatic islets (FIG 6). ..
  49. Astrand A, Bohlooly Y M, Larsdotter S, Mahlapuu M, Andersén H, Tornell J, et al. Mice lacking melanin-concentrating hormone receptor 1 demonstrate increased heart rate associated with altered autonomic activity. Am J Physiol Regul Integr Comp Physiol. 2004;287:R749-58 pubmed
    ..Administration of the adrenergic antagonist metoprolol completely reversed the tachycardia seen in MCHR1(-/-) mice, suggesting an increased sympathetic tone. ..
  50. Hertzog D, Al Barazanji K, Bigham E, Bishop M, Britt C, Carlton D, et al. The discovery and optimization of pyrimidinone-containing MCH R1 antagonists. Bioorg Med Chem Lett. 2006;16:4723-7 pubmed
    ..Details of the optimization process are provided and the use of one of the compounds in an animal model of diet-induced obesity is presented. ..
  51. Jamen F, Bouschet T, Laden J, Bockaert J, Brabet P. Up-regulation of the PACAP type-1 receptor (PAC1) promoter by neurotrophins in rat PC12 cells and mouse cerebellar granule cells via the Ras/mitogen-activated protein kinase cascade. J Neurochem. 2002;82:1199-207 pubmed
    ..Our results show that the PAC1 promoter can be up-regulated by diverse neurotrophins via an MAPK-dependent pathway and suggest a role for the Ras protein. ..
  52. Veitch C, Brown L, Sernia C, Gemmell R. Role of PGF2alpha and oxytocin in parturition in the brushtail possum (Trichosurus vulpecula). Reproduction. 2002;123:429-34 pubmed
    ..Low numbers of PGF(2alpha) receptors were found in the possum corpus luteum at birth, indicating an involvement of PGF(2alpha) in regression of the corpus luteum. ..
  53. Knudsen S, Tams J, Fahrenkrug J. Role of second extracellular loop in the function of human vasoactive intestinal polypeptide/pituitary adenylate cyclase activating polypeptide receptor 1 (hVPAC1R). J Mol Neurosci. 2000;14:137-46 pubmed
    ..These results indicate that some residues in the second extracellular loop of the human VPAC1R participate in the active mechanism of a ligand-mediated response without being directly involved in the binding of VIP. ..