GAP JUNCTION COMMUNICATION MODULATES [CA2-SECRETION IN PANCREATIC ACINI(]I OSCILLATIONS AND ENZYME)

Global (all cells in an acinus) and focal (1-2 out of 10-15 cells) sti mulation of pancreatic acini with bombesin or oxycarbonyl-Tyr(SO3)-Nle -Gly-Tyr-Asp-2-phenylethyl ester (CCKJ) together with modulation of ga p junction (GJ) permeability by octanol and NO2- was used to study the role of GJ permeability in controlling [Ca2+]i oscillations and enzym e secretion. GJ permeability was quantitated by measuring fluorescence recovery after photobleaching. Octanol at 0.5 mM markedly reduced, wh ereas 15 mM NO2- increased GJ permeability. Focal application of bombe sin caused synchronized oscillations in the entire acinus, whereas glo bal stimulation resulted in asynchronous oscillations. Increasing GJ p ermeability with NO2- had no effect on bombesin-evoked [Ca2+]i oscilla tions. Octanol inhibited ongoing oscillations evoked by focal or globa l bombesin stimulation. However, when GJ were blocked prior to stimula tion, subsequent global stimulation with bombesin induced long-lasting oscillations in all cells. Re-establishing GJ communication for as li ttle as 37.5 s conferred GJ dependence on the order and time of [Ca2+] i spiking evoked by global bombesin stimulation. Focal and global stim ulation with CCKJ gave different patterns of [Ca2+]i oscillations. How ever, in contrast to bombesin, inhibition of GJ with octanol had no ef fect on oscillations induced by global CCKJ stimulation. Increasing GJ permeability with NO2- synchronized CCKJ-stimulated oscillations by e qualizing the amplitude and increasing the frequency in all cells with in an acinus. These observations suggest that amplitude and frequency of [Ca2+]i oscillations can be regulated independently of each other, and that GJ permeable molecules modulate the frequency of [Ca2+]i osci llation in an agonist-specific manner. Regardless of the agonist, incr easing the frequency of oscillations by modulation of GJ permeability correlated with an increased enzyme secretion.