Hypotensive effects of ghrelin receptor agonists mediated through a novel receptor

Callaghan, Brid, Kosari, Samin, Pustovit, Ruslan V., Sartor, Daniela M., Ferens, Dorota, Ban, Kung, Baell, Jonathan, Nguyen, Trung V., Rivera, Leni R., Brock, James A. and Furness, John B. 2014, Hypotensive effects of ghrelin receptor agonists mediated through a novel receptor, British journal of pharmacology, vol. 171, no. 5, Special Issue: Themed Section: Molecular Pharmacology of GPCRs, pp. 1275-1286, doi: 10.1111/bph.12527.

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Title Hypotensive effects of ghrelin receptor agonists mediated through a novel receptor
Author(s) Callaghan, Brid
Kosari, Samin
Pustovit, Ruslan V.
Sartor, Daniela M.
Ferens, Dorota
Ban, Kung
Baell, Jonathan
Nguyen, Trung V.
Rivera, Leni R.
Brock, James A.
Furness, John B.
Journal name British journal of pharmacology
Volume number 171
Issue number 5
Season Special Issue: Themed Section: Molecular Pharmacology of GPCRs
Start page 1275
End page 1286
Total pages 12
Publisher Wiley-Blackwell
Place of publication Chichester, Eng.
Publication date 2014-03
ISSN 0007-1188
Keyword(s) ghrelin
phrelin receptors
Summary BACKGROUND AND PURPOSESome agonists of ghrelin receptors cause rapid decreases in BP. The mechanisms by which they cause hypotension and thepharmacology of the receptors are unknown.EXPERIMENTAL APPROACHThe effects of ligands of ghrelin receptors were investigated in rats in vivo, on isolated blood vessels and on cells transfectedwith the only molecularly defined ghrelin receptor, growth hormone secretagogue receptor 1a (GHSR1a).KEY RESULTSThree agonists of GHSR1a receptors, ulimorelin, capromorelin and CP464709, caused a rapid decrease in BP in theanaesthetized rat. The effect was not reduced by either of two GHSR1a antagonists, JMV2959 or YIL781, at doses thatblocked effects on colorectal motility, in vivo. The rapid hypotension was not mimicked by ghrelin, unacylated ghrelin orthe unacylated ghrelin receptor agonist, AZP531. The early hypotension preceded a decrease in sympathetic nerve activity.Early hypotension was not reduced by hexamethonium or by baroreceptor (sino-aortic) denervation. Ulimorelin also relaxedisolated segments of rat mesenteric artery, and, less potently, relaxed aorta segments. The vascular relaxation was not reducedby JMV2959 or YIL781. Ulimorelin, capromorelin and CP464709 activated GHSR1a in transfected HEK293 cells at nanomolarconcentrations. JMV2959 and YIL781 both antagonized effects in these cells, with their pA2 values at the GHSR1a receptorbeing 6.55 and 7.84.CONCLUSIONS AND IMPLICATIONSOur results indicate a novel vascular receptor or receptors whose activation by ulimorelin, capromorelin and CP464709lowered BP. This receptor is activated by low MW GHSR1a agonists, but is not activated by ghrelin.
Language eng
DOI 10.1111/bph.12527
Field of Research 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
1115 Pharmacology And Pharmaceutical Sciences
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2013, British Pharmacological Society
Persistent URL http://hdl.handle.net/10536/DRO/DU:30079266

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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