Correlation between phospholipid breakdown, intracellular calcium mobulization and enzyme secretion in rat pancreatic acini treated with Boc-[Nle 28, Nle 31]-CCK-7 and JMV180, two cholecystokinin analogues

Abstract

In this work in vitro pharmacological profiles of two analogues of the C-terminal heptapeptide of cholecystokinin (CCK) were evaluated. The analogue Boc-[Nle 28, Nle 31]-CCK-7, a stable analogue of CCK-8, has the same activity profile as CCK-8, and was found to be very potent in stimulating amylase secretion, phospholipid breakdown and [Ca 2+] i mobilization from rat pancreatic acini. It can be used as a probe for studying CCK-actions. The CCK-analogue Boc-Tyr(SO 3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethylester, (JMV180), which stimulates amylase secretion without inhibition at supramaximal concentrations, has different effects on phospholipid hydrolysis and [Ca 2+] i mobilization, compared to CCK-8 and Boc-[Nle 28, NLE 31]-CCk-7. Compound JMV180 was unable to significantly promote phospholipid breakdown, and was only 50%–60% as efficacious as Boc-[Nle 28, Nle 31]-CCK-7 in promoting [Ca 2+] i mobilization. These findings suggest that low affinity CCK-receptors might be responsible for the supra-maximal inhibition of amylase secretion, and are correlated with phospholipid breakdown and maximal [Ca 2+] i mobilization.