Cholecystokinin analog JMV-180-induced intracellular calcium oscillations are mediated by inositol 1,4,5-trisphosphate in rat pancreatic acini.

AIM: To investigate whether inositol 1,4,5-trisphosphate (IP3) is involved in secretory response of pancreatic acini to cholecystokinin (CCK) analog Boc-Tyr (SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethylester.2NH3 (JMV-180). METHODS: Dynamics of cytosolic Ca2+ concentration, [Ca2+]c, was recorded by ratiometry of Fura-2 in pancreatic acini. RESULTS: In perfused preparations of isolated rat pancreatic acinar cells, 2-aminoethoxydiphenylborate (2APB), a new membrane permeant inhibitory modulator of IP3-mediated calcium release from internal stores, inhibited JMV-180-induced [Ca2+]c spikes, and 2APB at 100 mumol.L-1 resulted in an immediate, complete inhibition of the spikes. CONCLUSION: Recurrent [Ca2+]c spikes induced by continuous stimulation with JMV-180 are initiated via IP3-mediated Ca2+ release from internal Ca2+ stores.