Sustained cholecystokinin-B/gastrin receptor blockade does not impair basal or histamine-stimulated acid secretion in chronic gastric fistula rats.
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.
Ding
X Q
XQ
Department of Pharmacology, University of Lund, Sweden.
Kitano
M
M
Håkanson
R
R
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D002766:Cholecystokinin / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism*; D005747:Gastric Fistula / Q000378:metabolism*; D005755:Gastrins / Q000097:blood* / Q000378:metabolism; D006632:Histamine / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*
D005755:Gastrins; D006727:Hormone Antagonists; D011949:Receptors, Cholecystokinin; D001569:Benzodiazepines; C087260:YM 022; D006632:Histamine; D002766:Cholecystokinin