AJP - Gastrointestinal and Liver Physiology, Vol 269, Issue 5 699-G705, Copyright © 1995 by American Physiological Society
Gastrin receptor antagonist YM022 prevents hypersecretion after long-term acid suppression
A. Nishida, A. Kobayashi-Uchida, S. Akuzawa, Y. Takinami, T. Shishido, T. Kamato, H. Ito, M. Yamano, H. Yuki, Y. Nagakura and al. et
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd., Ibaraki, Japan.
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.
