Inhibition of gastric acid secretion by human calcitonin gene-related peptide with picomolar potency in guinea-pig parietal cell preparations.
The effect of CGRP on [14C]-aminopyrine accumulation in isolated parietal cell preparations from guinea-pig fundic mucosa was studied. Parietal cells consisted of 60% of the preparations. [14C]-Aminopyrine accumulation was used as an index of physiological response of parietal cells to secretagogues. CGRP dose-dependently (10(-12)-10(-9) M) inhibited parietal cell aminopyrine accumulation stimulated by histamine (10(-4) M), carbachol (10(-4) M), and pentagastrin (5 X 10(-6) M). The concentration of CGRP exerting half-maximal inhibition of [14C]-aminopyrine accumulation was 8.7 X 10(-11) M for histamine, 9.1 X 10(-11) M for carbachol, and 4.7 X 10(-11) M for pentagastrin. The inhibitory effect was much more potent than cimetidine, pirenzepine or benzotript. CGRP but not cimetidine inhibited DBcAMP stimulated aminopyrine accumulation (IC50 = 7.5 X 10(-11) M). These results suggest that CGRP may exert its inhibitory action on gastric acid secretion by a direct action on the parietal cell or the somatostatin-producing D cell.
D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide; D002927:Cimetidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000378:metabolism; D010890:Pirenzepine / Q000494:pharmacology
D001549:Benzamides; D009479:Neuropeptides; D000632:Aminopyrine; D010890:Pirenzepine; D002927:Cimetidine; D006632:Histamine; D015740:Calcitonin Gene-Related Peptide; C013841:benzotript