Agonist-regulated alteration of the affinity of pancreatic muscarinic cholinergic receptors.

摘要: Heterologous desensitization is a term that indicates exposure of cell to an agonist attenuates the response other agonists. We examined heterologous muscarinic cholinergic receptors pancreatic acini and characterized mechanisms might be responsible for desensitization. Muscarinic receptor binding was measured by using N-[3H]methscopolamine bromide ([3H]NMS). N-Methscopolamine (NMS), antagonist, bound single class with affinity 0.22 +/- 0.04 nM capacity 61.5 5.1 fmol/mg protein. These parameters NMS sites were not altered addition cholecystokinin (CCK) octapeptide, CCK-JMV-180, vasoactive intestinal peptide, 8-bromo-cAMP, 4-bromo-A23187, thapsigargin, or 12-O-tetradecanoylphorbol-13-acetate (TPA). Analysis competitive inhibition curve [3H] carbachol showed apparently two classes high (38.6%) low (61.4%). Simultaneous incubation CCK TPA increased relative [3H]NMS binding, curves site. L-364,718 blocked effect CCK, staurosporine effects partially CCK. thapsigargin had no on binding. Second, carbachol-induced sequestration examined. Incubation resulted in decrease sites, caused disappearance sites. Finally, studies biological acinar cells biphasic amylase release completely suppressed 10 entire range carbachol. Taken together, these results suggest important alteration apparent Further, another factor induces uncoupling from effector involved agonist-regulated The results, CCK-JMV-180 agonists activate adenylate cyclase pathway did exert protein kinase C may one key factors suppression release.