Pharmacological evidence for the involvement of multiple calcitonin gene-related peptide (CGRP) receptors in the antisecretory and antiulcer effect of CGRP in rat stomach.
We have investigated the effect of the C-terminal fragment of human calcitonin gene-related peptide (human-CGRP8-37), a CGRP antagonist, on alpha-CGRP and salmon Calcitonin (sCT)-induced inhibition of gastric acid secretion stimulated by pentagastrin (24 nmol kg-1 h-1 i.v.) and gastric lesions induced by acetylsalycilic acid (ASA; 25 mM) in rats anaesthetized with urethane. Close intra arterial infusion of alpha-CGRP (2-5 nmol kg-1) and sCT (5 nmol kg-1) produced a reduction in gastric acid hypersecretion induced by pentagastrin. The concomitant infusion with human-CGRP8-37 (10 nmol kg-1) reversed the effect of both agonists. ASA-ulcers were reduced in a dose-dependent manner by infusion of alpha-CGRP (1-2 nmol kg-1 i.a.), but not by sCT (10 nmol kg-1 i.a.). Human-CGRP8-37 at a dose of 10 nmol kg-1 i.a. was unable to reverse the alpha-CGRP antiulcer effect. An higher dose of human-CGRP8-37 (50 nmol kg-1 i.a.) showed agonistic properties reducing ASA ulcers. These results suggest that the inhibitory effects of alpha-CGRP on stimulated acid secretion and aspirin ulcers are mediated by different mechanisms and/or different receptors.
Evangelista
S
S
Pharmacology Department, Malesci Pharm., Firenze, Italy.
Tramontana
M
M
Maggi
C A
CA
D000818:Animals; D002116:Calcitonin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000494:pharmacology*; D005750:Gastric Juice / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000502:physiology*; D012636:Secretory Rate / Q000187:drug effects; D013270:Stomach / Q000503:physiopathology; D013276:Stomach Ulcer / Q000517:prevention & control*
D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide