title: Central action of adrenomedullin to inhibit gastric emptying in rats.
abstract: The central action of human adrenomedullin (AM) to influence gastric emptying and the peripheral mechanisms involved were studied in conscious rats. The 20-min rate of gastric emptying of a methylcellulose solution was assessed after intracisternal (i.c.) injection of AM or rat alpha-calcitonin gene-related peptide (alphaCGRP). AM and alphaCGRP dose-dependently inhibited gastric emptying with i.c. ED50 values of 120 and 100 pmol, respectively. Human proadrenomedullin N-terminal 20 peptide (150-600 pmol, i.c.) and AM (150 pmol, i.v.) had no effect. The inhibitory actions of AM and alphaCGRP (150 pmol, i.c.) were completely blocked by the CGRP antagonist, human CGRP-(8-37) injected i.c. at 30 microg, but not at 15 microg. The CRF antagonist, [D-Phe12,Nle(21,38),C(alpha)MeLeu37]CRF-(12-41) (10 microg/rat) injected i.c. prevented i.c. rat/human CRF (150 pmol)-induced 53% inhibition of gastric emptying while not modifying the effect of AM. The action of AM (150 pmol, i.c.) was abolished by bilateral adrenalectomy or the beta-adrenergic blocker, propranolol (1 mg/kg, i.p.), but was not altered by indomethacin (5 mg/kg, i.p.) or subdiaphragmatic vagotomy. These results indicate that i.c. AM and alphaCGRP equipotently inhibit gastric emptying through mechanisms similarly antagonized by a high dose of CGRP-(8-37). The central AM action is mediated through adrenal-dependent, beta-adrenergic pathways independently from activation of central CRF receptors.
authors.affiliation: CURE: Digestive Diseases Research Center, West Los Angeles Veterans Administration Medical Center, Department of Medicine and Brain Research Institute, University of California School of Medicine, 90073, USA. vmartine@ucla.edu
authors.forename: V
authors.initials: V
authors.lastname: Martínez
authors.forename: F
authors.initials: F
authors.lastname: Cuttitta
authors.forename: Y
authors.initials: Y
authors.lastname: Taché
mesh_terms: D000315:Adrenalectomy; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D053607:Adrenomedullin; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005746:Gastric Emptying / Q000187:drug effects*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008747:Methylcellulose / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014628:Vagotomy
chemical_list: D000319:Adrenergic beta-Antagonists; D010446:Peptide Fragments; D010455:Peptides; C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; D008747:Methylcellulose; D003346:Corticotropin-Releasing Hormone; D015740:Calcitonin Gene-Related Peptide; D007213:Indomethacin