Hypotensive effects of ghrelin receptor agonists mediated through a novel receptor

British Journal of Pharmacology

Volumn 171, Issue 5, 2014, Pages 1275-1286

  Callaghan, Brid ^a   Kosari, Samin ^a   Pustovit, Ruslan V ^a   Sartor, Daniela M ^a   Ferens, Dorota ^a   Ban, Kung ^b   Baell, Jonathan ^b   Nguyen, Trung V ^a   Rivera, Leni R ^a   Brock, James A ^a   Furness, John B ^a  

^a UNIVERSITY OF MELBOURNE   (Australia)

^b MONASH UNIVERSITY   (Australia)

Author keywords

BP; ghrelin; ghrelin receptors; vasodilation

Indexed keywords

AZP 531; CAPROMORELIN; CP 464709; GROWTH HORMONE RELEASING FACTOR DERIVATIVE; GSK 894490; HEXAMETHONIUM; JMV 2959; ULIMORELIN; UNCLASSIFIED DRUG; YIL 781;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANTIHYPERTENSIVE ACTIVITY; AORTA; ARTICLE; BLOOD PRESSURE MEASUREMENT; COLON; CONTINUOUS INFUSION; CONTROLLED STUDY; DENERVATION; DOSE RESPONSE; DRUG MECHANISM; DRUG POTENCY; HYPOTENSION; IN VIVO STUDY; INTESTINE MOTILITY; MALE; MESENTERIC ARTERY; NONHUMAN; PRESSORECEPTOR; PRIORITY JOURNAL; RAT; RECTUM; SYMPATHETIC NERVE; VASODILATATION;

BP; GHRELIN; GHRELIN RECEPTORS; VASODILATION;

ANIMALS; AORTA, THORACIC; BLOOD PRESSURE; GHRELIN; HEK293 CELLS; HUMANS; HYPOTENSION; MACROCYCLIC COMPOUNDS; MALE; MESENTERIC ARTERIES; PIPERIDINES; PYRAZOLES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, GHRELIN;

EID: 84895084993     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.12527     Document Type: Article

References (55)

1. Akamizu T, Kangawa K, (2012). The physiological significance and potential clinical applications of ghrelin. Eur J Int Med 23: 197-202.
2. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, et al. (2013). The concise guide to PHARMACOLOGY 2013/14: G protein-coupled receptors. Br J Pharmacol 170: 1459-1581.
3. Andrews ZB, (2011). The extra-hypothalamic actions of ghrelin on neuronal function. Trends Neurosci 34: 31-40.
4. Bogeski G, Shafton AD, Kitchener PD, Ferens DM, Furness JB, (2005). A quantitative approach to recording peristaltic activity from segments of rat small intestine in vivo. Neurogastroenterol Motil 17: 262-272.
5. Callaghan B, Hunne B, Hirayama H, Sartor DM, Nguyen TV, Abogadie FC, et al. (2012). Sites of action of ghrelin receptor ligands in cardiovascular control. Am J Physiol 303: H1011-H1021.
6. Camiña JP, (2006). Cell biology of the ghrelin receptor. J Neuroendocrinol 18: 65-76.
7. Carpino PA, Lefker BA, Toler SM, Pan LC, Hadcock JR, Cook ER, et al. (2003). Pyrazolinone-piperidine dipeptide growth hormone secretagogues (GHSs): discovery of capromorelin. Bioorg Med Chem 11: 581-590.
8. Chollet C, Meyer K, Beck-Sickinger AG, (2009). Ghrelin-a novel generation of anti-obesity drug: design, pharmacomodulation and biological activity of ghrelin analogues. J Pept Sci 15: 711-730.
9. Chollet C, Bergmann R, Pietzsch J, Beck Sickinger AG, (2012). Design, evaluation and comparison of ghrelin receptor agonists and inverse agonists as suitable radiotracers for PET imaging. Bioconj Chem 23: 771-784.
10. Chopin L, Walpole C, Seim I, Cunningham P, Murray R, Whiteside E, et al. (2011). Ghrelin and cancer. Mol Cell Endocrinol 340: 65-69.
11. Collister JP, Osborn JW, (1999). The chronic infusion of hexamethonium and phenylephrine to effectivelyclamp sympathetic vasomotor tone: a novel approach. J Pharmacol Toxicol Methods 42: 135-147.
12. DeBoer MD, (2011). Ghrelin and cachexia: will treatment with GHSR-1a agonists make a difference for patients suffering from chronic wasting syndromes? Mol Cell Endocrinol 340: 97-105.
13. Delhanty PJD, van Koetsveld PM, Gauna C, van de Zande B, Vitale G, Hofland LJ, et al. (2007). Ghrelin and its unacylated isoform stimulate the growth of adrenocortical tumor cells via an anti-apoptotic pathway. Am J Physiol 293: E302-E309.
14. Delhanty PJD, Neggers SJ, van der Lely AJ, (2012). Ghrelin: the differences between acyl- and des-acyl ghrelin. Eur J Endocrinol 167: 601-608.
15. Ejskjaer N, Dimcevski G, Wo J, Hellström PM, Gormsen LC, Sarosiek I, et al. (2010). Safety and efficacy of ghrelin agonist TZP-101 in relieving symptoms in patients with diabetic gastroparesis: a randomized, placebo-controlled study. Neurogastroenterol Motil 22: 1069-1281.
16. Esler WP, Rudolph J, Claus TH, Tang W, Barucci N, Brown S-E, et al. (2007). Small-molecule ghrelin receptor antagonists improve glucose tolerance, suppress appetite, and promote weight loss. Endocrinology 148: 5175-5185.
17. Ferens DM, Chang EC, Bogeski G, Shafton AD, Kitchener PD, Furness JB, (2005). Motor patterns and propulsion in the rat intestine in vivo recorded by spatio-temporal maps. Neurogastroenterol Motil 17: 714-720.
18. Ferens DM, Yin L, Bron R, Hunne B, Ohashi-Doi K, Sanger GJ, et al. (2010). Functional and in situ hybridisation evidence that preganglionic sympathetic vasoconstrictor neurons express ghrelin receptors. Neuroscience 166: 671-679.
19. Ferens DM, Habgood MD, Saunders NR, Tan YH, Brown DJ, Brock JA, et al. (2011). Stimulation of defecation in spinal cord-injured rats by a centrally acting ghrelin receptor agonist. Spinal Cord 49: 1036-1041.
20. Furness JB, Hunne B, Matsuda N, Yin L, Russo D, Kato I, et al. (2011). Investigation of the presence of ghrelin in the central nervous system of the rat and mouse. Neuroscience 193: 1-9.
21. Garcia JM, Friend J, Allen S, (2013). Therapeutic potential of anamorelin, a novel, oral ghrelin mimetic, in patients with cancer-related cachexia: a multicenter, randomized, double-blind, crossover, pilot study. Support Care Cancer 21: 129-137.
22. Gauna C, Delhanty PJD, Hofland LJ, Janssen JAMJL, Broglio F, Ross RJM, et al. (2005). Ghrelin stimulates, whereas des-octanoyl ghrelin inhibits, glucose output by primary hepatocytes. J Clin Endocrinol Metab 90: 1055-1060.
23. Gauna C, van de Zande B, van Kerkwijk A, Themmen APN, van der Lely AJ, Delhanty PJD, (2007). Unacylated ghrelin is not a functional antagonist but a full agonist of the type 1a growth hormone secretagogue receptor (GHS-R). Mol Cell Endocrinol 274: 30-34.
24. Granata R, Settanni F, Julien M, Nano R, Togliatto G, Trombetta A, et al. (2012). Des-acyl ghrelin fragments and analogues promote survival of pancreatic β-cells and human pancreatic islets and prevent diabetes in streptozotocin-treated rats. J Med Chem 55: 2585-2596.
25. Hassouna R, Labarthe A, Zizzari P, Videau C, Culler M, Epelbaum J, et al. (2013). Actions of agonists and antagonists of the ghrelin/GHS-R pathway on GH secretion, appetite, and cFos activity. Front Endocrinol 4: 1-9.
26. Hirayama H, Shiina T, Shima T, Kuramoto H, Takewaki T, Furness JB, et al. (2010). Contrasting effects of ghrelin and des-acyl ghrelin on the lumbo-sacral defecation center and regulation of colorectal motility in rats. Neurogastroenterol Motil 22: 1124-1131.
27. Hoveyda HR, Marsault E, Gagnon R, Mathieu AP, Vézina M, Landry A, et al. (2011). Optimization of the potency and pharmacokinetic properties of a macrocyclic ghrelin receptor agonist (Part I): development of ulimorelin (TZP-101) from hit to clinic. J Med Chem 54: 8305-8320.
28. How JMY, Pumpa TJ, Sartor DM, (2013). The circulatory and renal sympathoinhibitory effects of gastric leptin are altered by a high fat diet and obesity. Auton Neurosci 117: 95-100.
29. Isgaard J, Granata R, (2011). Ghrelin in cardiovascular disease and atherogenesis. Mol Cell Endocrinol 340: 59-64.
30. Julien M, Kay RG, Delhanty PJD, Allas S, Granata R, Barton C, et al. (2012). In vitro and in vivo stability and pharmacokinetic profile of unacylated ghrelin (UAG) analogues. Eur J Pharm Sci 47: 625-635.
31. Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG, (2010). Animal research: Reporting in vivo experiments: the ARRIVE guidelines. Br J Pharmacol 160: 1577-1579.
32. Kojima M, Kangawa K, (2010). Ghrelin: more than endogenous growth hormone secretagogue. Ann N Y Acad Sci 1200: 140-148.
33. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K, (1999). Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402: 656-660.
34. Li L, Zhang L-K, Pang Y-Z, Pan C-S, Qi Y-F, Chen L, et al. (2006). Cardioprotective effects of ghrelin and des-octanoyl ghrelin on myocardial injury induced by isoproterenol in rats. Acta Pharmacol Sin 27: 527-535.
35. McDonald DM, (1983). Morphology of the rat carotid sinus nerve.I. Course, connections, dimensions and ultrastructure. J Neurocytol 12: 345-372.
36. McGrath J, Drummond G, McLachlan E, Kilkenny C, Wainwright C, (2010). Guidelines for reporting experiments involving animals: the ARRIVE guidelines. Br J Pharmacol 160: 1573-1576.
37. Matsumura K, Tsuchihashi T, Fujii K, Abe I, Iida M, (2002). Central ghrelin modulates sympathetic activity in conscious rabbits. Hypertension 40: 694-699.
38. Mulvany MJ, Halpern W, (1977). Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats. Circ Res 41: 19-26.
39. Myers PR, Minor RL, Jr, Guerra R, Jr, Bates JN, Harrison DG, (1990). Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble S-nitrosocysteine than nitric oxide. Nature 345: 161-163.
40. Nagaya N, Kojima M, Uematsu M, Yamagishi M, Hosoda H, Oya H, et al. (2001). Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am J Physiol 280: R1483-R1487.
41. Nass R, Gaylinn BD, Thorner MO, (2011). The ghrelin axis in disease: potential therapeutic indications. Mol Cell Endocrinol 340: 106-110.
42. Okumura H, Nagaya N, Enomoto M, Nakagawa E, Oya H, Kangawa K, (2002). Vasodilatory effect of ghrelin, an endogenous peptide from the stomach. J Cardiovasc Pharmacol 39: 779-783.
43. Ross G, Chaudhuri G, Ignarro LJ, Chyu KY, (1991). Acetylcholine vasodilation of resistance vessels in vivo may not entirely depend on newly synthesized nitric oxide. Eur J Pharmacol 195: 291-293.
44. Salomé N, Haage D, Perrissoud D, Moulin A, Demange L, Egecioglu E, et al. (2009). Anorexigenic and electrophysiological actions of novel ghrelin receptor (GHS-R1A) antagonists in rats. Eur J Pharmacol 612: 167-173.
45. Seim I, Josh P, Cunningham P, Herington A, Chopin L, (2011). Ghrelin axis genes, peptides and receptors: recent findings and future challenges. Mol Cell Endocrinol 340: 3-9.
46. Shimizu Y, Chang EC, Shafton AD, Ferens DM, Sanger GJ, Witherington J, et al. (2006). Evidence that stimulation of ghrelin receptors in the spinal cord initiates propulsive activity in the colon of the rat. J Physiol (Lond) 576: 329-338.
47. Shimokawa H, Yasutake H, Fujii K, Owada MK, Nakaike R, Fukumoto Y, et al. (1996). The importance of the hyperpolarizing mechanism increases as the vessel size decreases in endothelium-dependent relaxations in rat mesenteric circulation. J Cardiovasc Pharmacol 28: 703-711.
48. Thompson NM, Gill DAS, Davies R, Loveridge N, Houston PA, Robinson ICAF, et al. (2004). Ghrelin and des-octanoyl ghrelin promote adipogenesis directly in vivo by a mechanism independent of the type 1a growth hormone secretagogue receptor. Endocrinology 145: 234-242.
49. Toshinai K, Yamaguchi H, Sun Y, Smith RG, Yamanaka A, Sakurai T, et al. (2006). Des-acyl ghrelin induces food intake by a mechanism independent of the growth hormone secretagogue receptor. Endocrinology 147: 2306-2314.
50. Tsubota Y, Owada-Makabe K, Yukawa K, Maeda M, (2005). Hypotensive effect of des-acyl ghrelin at nucleus tractus solitarii of rat. Neuroreport 16: 163-166.
51. Van Der Lely AJ, Tschöp M, Heiman ML, Ghigo E, (2004). Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr Rev 25: 426-457.
52. Warzecha Z, Dembinski A, (2012). Protective and therapeutic effects of ghrelin in the gut. Curr Med Chem 19: 118-125.
53. White HK, Petrie CD, Landschulz W, MacLean D, Taylor A, Lyles K, et al. (2009). Effects of an oral growth hormone secretagogue in older adults. J Clin Endocrinol Metab 94: 1198-1206.
54. Witherington J, Abberley L, Briggs MA, Collis K, Dean DK, Gaiba A, et al. (2008). Potent achiral agonists of the growth hormone secretagogue (ghrelin) receptor. Part 2: lead optimisation. Bioorg Med Chem Lett 18: 2203-2205.
55. Zygmunt PM, Ryman T, Högestätt ED, (1995). Regional differences in endothelium-dependent relaxation in the rat: contribution of nitric oxide and nitric oxide-independent mechanisms. Acta Physiol Scand 155: 257-266.