CGRP antagonists enhance gastric acid secretion in 2-h pylorus-ligated rats.
The influence of calcitonin gene-related peptide (CGRP) antagonists on gastric acid secretion was investigated in rats. Intravenous injection of the CGRP receptor antagonist, CGRP(8-37) (128 nmol/kg) or the CGRP antibody #4901 (4.8 mg/kg, IV) completely prevented alpha-CGRP (3.9 nmol/kg/h)-induced inhibition of acid response to pentagastrin in urethane-anesthetized rats with gastric fistula. CGRP antibody (4.8 mg/kg, IV) increased by 93% gastric acid secretion in conscious rats with pylorus ligation for 2 h. (CGRP(8-73) (128 nmol/kg, IV) also enhanced the acid response measured 2 h after pylorus ligation in conscious rats and in urethane-anesthetized rats infused with pentagastrin by 91% and 56%, respectively. These results suggest that endogenous CGRP attenuates the gastric acid response measured 2 h after pylorus ligation.
Kato
K
K
CURE/UCLA Gastroenteric Biology Center, VA Wadsworth Medical Center 90073, USA.
Martinez
V
V
St Pierre
S
S
Taché
Y
Y
D000758:Anesthesia; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000494:pharmacology; D002404:Catheterization; D003243:Consciousness; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005744:Gastric Acid / Q000378:metabolism*; D005747:Gastric Fistula; D008026:Ligation; D008297:Male; D010418:Pentagastrin / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011708:Pylorus / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D010418:Pentagastrin; D015740:Calcitonin Gene-Related Peptide