Muscarinic M2-receptors enhance polyphosphoinositol release in rat gastric mucosal cells

Abstract

Muscarinic receptor types and their effects on the inositol phosphate second messenger system were studied in enzymatically dispersed rat gastric mucosal cells. Radioreceptor binding studies indicated the presence of a single class of binding sites (4860 +/- 875 sites/cell) and affinities of 0.42 +/- 0.12 nM, 176 +/- 32 nM and 13 microM for N-methylscopolamine, pirenzepine and carbachol, respectively. In cells prelabelled with myo-[3H]inositol carbachol induced a dose-dependent increase in inositol-1-phosphate in the presence of lithium with an ED50 of 10 microM which was antagonized by atropine and pirenzepine (IC50 9 and 700 nM, respectively). Carbachol stimulated amino[14C]pyrine uptake, used as a measure of acid secretion, with an ED50 of 10 microM. The good correlation between these responses suggests a role for inositol phosphates in the muscarinic M2-receptor mediated acid secretion.