REGULATION OF GAP JUNCTIONAL COUPLING IN ISOLATED PANCREATIC ACINAR CELL PAIRS BY CHOLECYSTOKININ-OCTAPEPTIDE, VASOACTIVE-INTESTINAL-PEPTIDE (VIP) AND A VIP-ANTAGONIST

Cholecystokinin-octapeptide (CCK-OP) induces a time- and dose-dependen t decrease of gap junctional conductance in isolated pairs of pancreat ic acinar cells. In double whole-cell experiments, the time course cou ld be described by the latency and the half-life time ttl,,) of cell-t o-cell uncoupling. The latency shows a biphasic dependence on [CCK-OP] with a minimum of about 50 sec at 10(-9) M CCK-OP. In the presence of vasoactive intestinal peptide (VIP), the biphasic relationship is shi fted to lower CCK-OP concentrations. The increase of latency at high c oncentrations of CCK-OP (>10(-9) M) was blocked by addition of a VIP-a ntagonist. t(1/2) decreases monophasically with increasing [CCK-OP]. A ddition of GTP gamma S to the pipette solution suppresses the [CCK-OP] dependence of the latency and potentiates the uncoupling phase. The k inetic data are discussed in terms of CCK binding to receptors of high and low affinity. Evidence is presented that secretion and cell-to-ce ll coupling are not related by an all-or-none process, but that for ph ysiological CCK-OP concentrations, gap junctional uncoupling follows s ecretion.