AJP - Gastrointestinal and Liver Physiology, Vol 248, Issue 2 184-G187, Copyright © 1985 by American Physiological Society
Pirenzepine-sensitive muscarinic receptors regulate gastric somatostatin and gastrin
R. Sue, M. L. Toomey, A. Todisco, A. H. Soll and T. Yamada
Pirenzepine, a newly described antagonist of selective muscarinic receptors
(M1), has been shown to be a potent inhibitor of acid secretion. To
determine whether this property of pirenzepine can be explained in part by
its actions on hormones regulating acid secretion, we examined
pirenzepine's effects on gastrin and somatostatinlike immunoreactivity
(SLI) secretion from the isolated, perfused rat stomach. Carbachol at a
dose of 10(-6) M inhibited SLI and stimulated gastrin secretion. Both
atropine and pirenzepine reversed these effects in a dose-dependent fashion
with D50 values of 1 X 10(-9) and 1 X 10(-7) M, respectively, against
gastrin stimulation and 1 X 10(-8) and 1 X 10(-7) M, respectively, against
SLI inhibition. Pirenzepine caused a progressive parallel rightward shift
in the dose-response curves for SLI inhibition and gastrin stimulation by
carbachol, suggesting competitive inhibition. The apparent inhibitory
constant (ki) was calculated to be approximately 2 X 10(-9) M. These
results indicate that gastrin and SLI release from the stomach is governed
by high-affinity muscarinic receptors that are sensitive to pirenzepine.
Pirenzepine's action as an acid secretory inhibitor, and possibly as an
ulcer therapy drug, may be explained in part by these effects on gastric
hormone regulation.
