AJP - Gastrointestinal and Liver Physiology, Vol 245, Issue 6 760-G768, Copyright © 1983 by American Physiological Society
Muscarinic receptors and guanylate cyclase in mammalian gastric glandular cells
D. J. Culp, J. M. Wolosin, A. H. Soll and J. G. Forte
To investigate the involvement of guanosine 3',5'-cyclic monophosphate
(cGMP) in the cholinergic activation of gastric acid and pepsinogen
secretion, we studied the subcellular and cellular relation between
particulate guanylate cyclase and muscarinic cholinergic receptor sites.
Subcellular fractionation of homogenates from rabbit gastric glands showed
that particulate guanylate cyclase and muscarinic receptors were
distributed in similar patterns, which differed from the pattern found for
Na+-K+-ATPase, a marker for basal-lateral plasma membranes. Assuming a
basal-lateral membrane localization for particulate guanylate cyclase and
cholinergic receptors, these results suggested a heterogeneity of glandular
basal-lateral membranes. The distributions of these markers among fractions
enriched in isolated canine parietal or chief cells were also followed.
Na+-K+-ATPase correlated with parietal cell distribution (r = 0.86) and
guanylate cyclase with chief cell distribution (r = 0.76). The distribution
of quinuclidinyl benzilate (QNB) binding sites indicated association of
muscarinic receptors with both cell types. The similar subcellular and
cellular distributions of guanylate cyclase and QNB binding sites may
reflect a functional relationship of these markers in muscarinic-activated
pepsinogen secretion. As seen in most other tissues, gastric glandular
guanylate cyclase was not stimulated by various gastric secretagogues. We
found that small changes in Ca2+ concentration, within the micromolar
range, can regulate glandular guanylate cyclase activity. These results are
discussed in terms of the cholinergic activation of parietal and chief cell
function.
