Peripheral adrenomedullin inhibits gastric emptying through CGRP8-37 -sensitive receptors and prostaglandins pathways in rats.
The effects of intravenous (iv) adrenomedullin (AM) on gastric emptying were investigated in conscious rats. AM induced a maximal 50% inhibition of gastric emptying at a dose of 1.2 nmol/kg. AM was about two-fold less potent than alpha-calcitonin gene-related peptide (alpha-CGRP), which induced a similar 50% maximal inhibition of gastric emptying at 0.6 nmol/kg. Delayed gastric emptying induced by i.v. AM and alpha-CGRP was prevented by peripheral injection of the selective CGRP1 antagonist, CGRP8-37, and by pretreatment with indomethacin, while not altered by blockade of the sympathetic nervous system with propranolol. These data indicate that peripheral AM inhibits gastric emptying through the interaction with CGRP8-37 -sensitive receptors, likely CGRP1 receptors, and the recruitment of prostaglandin-dependent mechanisms.
Martinez
V
V
CURE: Digestive Diseases Research Center, Department of Medicine, David Geffen School of Medicine at UCLA, University of California Los Angeles and VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA. vicente.martinez@astrazeneca.com
Wang
L
L
Taché
Y
Y
D053607:Adrenomedullin; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000737:chemistry / Q000494:pharmacology*; D005746:Gastric Emptying / Q000187:drug effects*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D018003:Receptors, Calcitonin / Q000378:metabolism; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism
D010446:Peptide Fragments; D010455:Peptides; D011453:Prostaglandins; D011943:Receptors, Adrenergic, beta; D018003:Receptors, Calcitonin; D018015:Receptors, Calcitonin Gene-Related Peptide; C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; D015740:Calcitonin Gene-Related Peptide; D007213:Indomethacin