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.