CA2+ SIGNALING IN THE PANCREATIC ACINUS

Change in cytosolic free calcium ion concentration [Ca2+](c), resultin g from receptor activation by an appropriate agonist, functions as a c ardinal intracellular signaling in the stimulus-secretion coupling in a wide variety of secretory cells including the acini of the pancreas. Ratiometric imaging of [Ca2+](c) dynamics by UV-laser scanning confoc al microscopy led us to conclude that in the cholecystokinin (CCK)-8-i nduced recurrent [Ca2+](c), spiking increases initially in the basolat eral margin of the acinus and propagates to the luminal margin. [Ca2+] (c) in this initial cell increased rapidly and uniformly to the maximu m level. The decrease in [Ca2+](c) in the initial cell coincided with a small increase in [Ca2+](c) in the luminal regions of the bilateral neighboring cells followed by uniform maximal increase in [Ca2+](c) in these neighboring cells. A series of [Ca2+](c) dynamics was repeated to form recurrent Ca2+ spiking. The temporal sequences of [Ca2+](c) dy namics recorded during continuous stimulation with CCK-8 at a physiolo gic concentration in individual acinar cells forming the acinus were d isplayed on the identical time scale. The figure indicates that the si gnaling is not synchronous in cells forming an acinus. From these and other results, we proposed a model in which CCK-8 at a low physiologic concentration binds to highly sensitive CCK receptor interacting with heterotrimeric guanosine 5'-triphosphate-binding proteins of the Gq c lass, generate Ins 1,4,5-P-3, and recurrent [Ca2+](c), spiking. The re current Ca2+ spiking maintains a sustained secretory response, recurre nt exocytosis of zymogen granules, and concomitant secretion of isoton ic NaCl.