Gastrin receptor antagonist YM022 prevents hypersecretion after long-term acid suppression.
Female rats were treated orally for 13 wk with YM022 (300 mumol.kg-1.day-1) and with omeprazole (400 mumol.kg-1.day-1) or famotidine (900 mumol.kg-1.day-1) with or without YM022. At 2 h after the last dose, YM022 and omeprazole markedly inhibited basal and pentagastrin-induced acid secretion. Famotidine was less potent than YM022 and omeprazole against both secretions. The degree of increase in plasma gastrin level in the three groups was parallel to the antisecretory potencies of the drugs. At 14 days after the cessation of omeprazole treatment, the secretory response to pentagastrin increased above that of the control. This hyperresponse lasted for > or = 56 days. In the famotidine-treated group, a small increase in secretory response to pentagastrin was observed but was not statistically significant. The increase in secretory response to pentagastrin was paralleled by an increase in mucosal cell mass. In contrast, YM022 not only exhibited a long-lasting inhibition of pentagastrin-induced acid secretion but also prevented the hyperresponse to pentagastrin caused by omeprazole. These results indicate that the hypergastrinemia caused by long-term administration of antisecretory drugs increases mucosal secretory response to pentagastrin through a gastrin/cholecystokinin B receptor-mediated pathway in rats.
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D002452:Cell Count; D004759:Enterochromaffin Cells / Q000166:cytology; D015738:Famotidine / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005755:Gastrins / Q000097:blood; D006632:Histamine / Q000378:metabolism; D006640:Histidine Decarboxylase / Q000378:metabolism; D009853:Omeprazole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D013997:Time Factors
D005755:Gastrins; D011949:Receptors, Cholecystokinin; D001569:Benzodiazepines; C087260:YM 022; D015738:Famotidine; D006632:Histamine; D006640:Histidine Decarboxylase; D009853:Omeprazole