The gastrin receptor antagonist ym022 prevents hyperresponse to
pentagastrin after prolonged inhibition of gastric acid
secretion.
Nishida, Akito, Ayumi Kobayashi-Uchida, Shinobu Akuzawa, Yusuke
Takinami, Takao Shishido, Takeshi Kamato, Hiroyuki Ito, Mayumi
Yamano, Hidenobu Yuki, Yukinor Nagakura, Kazuo Honda, and Keiji
Miyata.
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical
Co. Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305, Japan
APStracts 2:0120G, 1995.
Female rats were treated orally for 13 weeks with YM022 (300
mmol/kg/day), or with omeprazole (400 mmol/kg/day) or famotidine (900
mmol/kg/day) 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 these drugs against both
secretions. The degree of increase in plasma gastrin level in the
three groups was parallel to the antisecretory potencies of the
drugs. Fourteen days after the cessation of omeprazole, secretory
response to pentagastrin increased above that of the control. This
hyperresponse lasted for at least 56 days. In the famotidine-treated
group, a small increase in secretory response to pentagastrin was
observed, but this 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/CCK-B receptor-mediated
pathway in rats.
Received 29 November 1994; accepted in final form 18 May 1995.
APS Manuscript Number G467-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 July 1995.