Stimulus-secretion coupling and Ca2+ dynamics in pancreatic acinar cells.

1. Unique spatiotemporal dynamics in cytosolic Ca2+ concentration, [Ca2+]c, were characterized in various cell types. In pancreatic acinar cells, physiological concentrations of cholecystokinin octapeptide, CCK-8, (< 10 pM) induce repetitive [Ca2+]c spikes commonly termed Ca2+ oscillation, whereas relatively higher concentrations (30 pM-1 nM) evoke biphasic [Ca2+]c dynamics; a rapid transient peak followed by a sustained increase. Much higher concentrations (> 1 nM) induce a large transient followed by a steep decay. 2. These [Ca2+]c dynamics correspond to secretory responses. Repetitive [Ca2+]c change is attributable to the upstroke of the bell-shaped dose-response relationship and the biphasic change is responsible for the downstroke of the relation (so called high-dose inhibited secretion). The large transient [Ca2+]c increase is associated with morphological changes such as bleb formation. 3. Possible interrelation between dose of secretagogues, secretory responses, [Ca2+]c dynamics, IP3 production, receptor occupation and morphological change will be discussed from both pharmacological and physiological points of view.