Muscarinic receptors and guanylate cyclase in mammalian gastric glandular cells.
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.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D005088:Exocrine Glands / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000378:metabolism*; D017506:H(+)-K(+)-Exchanging ATPase; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008345:Manganese / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism
D011976:Receptors, Muscarinic; D008345:Manganese; D011813:Quinuclidinyl Benzilate; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D006162:Guanylate Cyclase; D000254:Sodium-Potassium-Exchanging ATPase; D008274:Magnesium; D002118:Calcium