Sustained cholecystokinin-B/gastrin receptor blockade does not impair basal or histamine-stimulated acid secretion in chronic gastric fistula rats.

Abstract	Gastrin is a physiologically important secretagogue. It is thought to stimulate parietal cells indirectly by mobilizing histamine from enterochromaffin-like (ECL) cells in the oxyntic mucosa. Gastrin stimulates the secretory activity and growth of the ECL cells via an action on cholecystokinin-B/gastrin receptors. Acute cholecystokinin-B/gastrin receptor blockade is known to inhibit gastrin-stimulated acid secretion but whether sustained cholecystokinin-B/gastrin receptor blockade will impair basal, gastrin- and histamine-stimulated acid secretion remains uncertain. The present study was designed to study the effect of long-term (4 weeks) cholecystokinin-B/gastrin receptor blockade on basal and stimulated acid secretion in conscious rats. The selective cholecystokinin-B/gastrin receptor antagonist YM022 (3 mumol.kg-1.hr-1) was given to gastric fistula rats by continuous subcutaneous infusion via osmotic minipumps for various times from 2 hr to 4 weeks. Basal, gastrin- and histamine-stimulated acid secretion were examined during and after cessation of treatment. Basal and histamine-stimulated acid secretion was not affected by YM022 during the 4 week period of administration, whereas gastrin-induced acid secretion was inhibited. YM022 induced hypergastrinaemia in freely fed rats but did not affect the serum gastrin level in fasted rats. The serum gastrin concentration and gastrin-induced acid secretion returned to control levels 3-7 days after termination of YM022 administration.
Authors	X Q Ding, M Kitano, R Håkanson
Journal	Pharmacology & toxicology (Pharmacol Toxicol) Vol. 82 Issue 4 Pg. 177-82 (Apr 1998) ISSN: 0901-9928 [Print] Denmark
PMID	9584331 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Gastrins Hormone Antagonists Receptors, Cholecystokinin Benzodiazepines YM 022 Histamine Cholecystokinin
Topics	Animals Benzodiazepines (pharmacology) Cholecystokinin (pharmacology) Gastric Acid (metabolism) Gastric Fistula (metabolism) Gastrins (blood, metabolism) Histamine (metabolism) Hormone Antagonists (pharmacology) Male Rats Rats, Sprague-Dawley Receptors, Cholecystokinin (antagonists & inhibitors)

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