Receptor occupation, calcium mobilization, and amylase release in pancreatic acini: effect of CCK-JMV-180

Publisher Website
Google Scholar
Abstract
We examined the relationships between receptor occupation, calcium mobilization, and stimulated amylase release for cholecystokinin octapeptide (CCK-8) and for CCK-JMV-180, an analogue of the COOH-terminal heptapeptide of CCK having the structure Boc-Tyr(SO3)-Nle-Gly-Trp-Nle-Asp-2-phenylethyl ester using dispersed acini from rat pancreas. CCK-8 and CCK-JMV-180 each bind to two classes of CCK receptors: one class has a high affinity for CCK-8 and CCK-JMV-180 and the other class has a low affinity for CCK-8 and CCK-JMV-180. Mobilization of cellular calcium was assessed by measuring cytosolic calcium with a fluorescent indicator and by measuring outflux of radioactive calcium from preloaded cells. In terms of causing an increase in cytosolic calcium or an increase in calcium outflux, CCK-JMV-180 was 50-60% as efficacious as CCK-8. Analysis of the relationship between receptor occupation and calcium mobilization caused by CCK-8 and CCK-JMV-180 in combination indicates that calcium mobilization is caused by occupation of low-affinity CCK receptors. Comparison of the dose-response curve for calcium mobilization and amylase release stimulated by CCK-8 or CCK-JMV-180 indicates that very low concentrations of each peptide stimulate amylase release without causing detectable calcium mobilization. At these very low concentrations, CCK-8 or CCK-JMV-180 do not cause potentiation of amylase release when combined with vasoactive intestinal peptide.