Sustained Cholecystokinin-B/Gastrin Receptor Blockade Does Not Impair Basal or Histamine-Stimulated Acid Secretion in Chronic Gastric Fistula Rats

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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 μmol · 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.

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