CGRP 8-37[correction of 8-27] blocks the inhibition of gastric emptying induced by intravenous injection of alpha-CGRP in rats.
The receptor subtype mediating rat alpha-calcitonin gene-related peptide (alpha-CGRP)-induced inhibition of gastric emptying of a non nutrient solution was tested in conscious rats using the CGRP1 receptor antagonist, CGRP 8-37, and the CCK antagonist, MK-329. Intravenous injection of alpha-CGRP (0.5 micrograms) decreased gastric emptying to 26.5 +/- 5.8% from 46.4 +/- 3.9% in vehicle-treated group. Intravenous injection of CGRP 8-37 (15 micrograms) did not influence gastric emptying but completely prevented alpha-CGRP inhibitory effect whereas the 47% delay in gastric emptying induced by intravenous cholecystokinin-8 (CCK, 0.25 microgram) was not modified. The CCK antagonist, MK-329 (1 mg) reversed CCK- but not alpha-CGRP-induced delay in gastric emptying. These results demonstrate that CGRP 8-37 is a specific tool to block alpha-CGRP inhibitory action on gastric motor function and suggest that gastric stasis elicited by peripheral injection of alpha-CGRP may involve an interaction with a CGRP1 receptor subtype.
Center for Ulcer Research and Education, VA Medical Center, Los Angeles, California.
V
V
Plourde
S
S
St-Pierre
A
A
Fournier
Y
Y
Taché
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors; D020109:Devazepide; D005746:Gastric Emptying / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*
D001570:Benzodiazepinones; D010446:Peptide Fragments; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; C058636:calcitonin gene-related peptide (8-37); D002766:Cholecystokinin; D020109:Devazepide; D015740:Calcitonin Gene-Related Peptide