Influence of extracellular [Ca2+] on secretory and redox responses to CCK-8 in perfused rat pancreas.

There is a distinct discrepancy between the dose-dependent secretory responses (pancreatic protein output and juice flow) and the dose-dependent redox responses of cytochromes aa3, b, and c+c1 to various concentrations of CCK-8: a bell-shaped relation for the secretory responses contrasts with a sigmoidal relation for the redox responses. Continuous stimulation with CCK-8 at physiological low concentrations (5-10 pM) induced an increase in pancreatic protein output with little if any reduction of cytochromes. Continuous stimulation with CCK-8 at a pharmacological intermediate concentration (50 pM), however, induced an increase in pancreatic protein output with delayed reduction of cytochromes. The secretory and redox responses were completely abolished when CaCl2 was removed from the perfusing and bathing solution. An almost linear relation was found between the magnitude of the protein output in response to 50 pM CCK-8 and extracellular [Ca2+] [( Ca2+]o) in the range of 0.5-2.5 mM. Similar relations were also found between the levels of reduction of cytochromes and [Ca2+]o. These results are compatible with the view that continuous stimulation with CCK-8 at a pharmacological or a pathological concentration may cause excess increase in intracellular [Ca2+] and intramitochondrial Ca2+ and in this way may accelerate the formation of reducing power for oxidative phosphorylation.