Intracellular control of IP3-independent Ca2+ oscillations in pancreatic acini

In pancreatic acini, the high affinity cholecystokinin (CCK)receptor agonist, CCK-OPE which utilizes the phospholipase A(2) (PLA(2))/arachidonic acid (AA) pathway, dose-dependently increased intracellular Ca2+ spike frequency and amplitude. An uncoupler of proton gradients, FCCP, abolished Ca2+ oscillations and amylase secretion induced by CCK-OPE. Furthermore, FCCP or decreasing extravesicular pH inhibited ATP-dependent Ca-45(2+) uptake into the endoplasmic reticulum (ER) fraction. On the other hand, cytosolic acidification induced by Na+-free medium led to Ca2+ oscillations. Depletion of intracellular ATP by antimycin resulted in an abolition of the response to CCK-OPE. Administration of the K+ ionophore, valinomycin, abolished the action of CCK-OPE. Decreasing K+ concentrations outside the ER vesicles inhibited ATP-dependent Ca-45(2+) uptake and AA-induced Ca-45(2+) release. Caffeine inhibited the actions of CCK-OPE, whereas ryanodine did not have any effects. These data suggest that IP3-independent Ca2+ oscillations mediated by the PLA, cascades involve the release of intracellular Ca2+ by AA and reuptake of Ca2+ by an ATP-dependent Ca2+/H+ antiport. Furthermore, the presence of a K+ membrane potential gradient across the ER membrane is required for normal Ca2+ oscillations. (C) 1996 Academic Press, Inc.