Properties of Intracellular Calcium Stores and Their Role in Receptor-Mediated Catecholamine Secretion in Rat Adrenal Chromaffin Cells

摘要

>Simulation of rat adrenal chromaffin cells either with receptor agonists such as muscarine, bradykinin and histamine or with caffeine in Ca2+-free Krebs solution induced a brief increase in the intracellular free Ca2+ concentration, [Ca2+]i, which terminated within 90 s. Both the agonist- and caffeine-induced [Ca2+]i responses were abolished in cells which had been treated with either 500 nM thapsigargin (TG) or 20 ?μM ryanodine, suggesting that inositol trisphosphate and caffeine cause Ca2+ release either from the same Ca2+ store or from distinct stores which exchange Ca2+ rapidly. In normal Krebs solution, these agonists evoked catecholamine (CA) secretion which showed an initial transient followed by a sustained component. Neither component of the secretion was significantly affected by TG or ryanodine. In the medium containing 16 ?μM Ca2+ or no Ca2+, CA secretion evoked by 30-second stimulation with 100 ?μM muscarine was 59 or 7%, respectively, of that evoked in the normal medium containing 2 mM Ca2+. In TG-treated cells, the CA secretion at 16 ?μM Ca2+ was reduced to 23% an what in the Ca2+-free medium was completely abolished. These results suggest that the receptor-mediated Ca2+ entry solely determines the rate of CA secretion in rat chromaffin cells when stimulated by receptor agonists in the normal medium, whereas intracellular Ca2+ release and Ca2+ entry may cooperatively support the secretion when cells are stimulated in media containing low concentrations of Ca2+.