[CA2-PIG CHROMAFFIN CELLS IN RESPONSE TO VARIOUS RECEPTOR AGONISTS AND THEIR RELATION TO CATECHOLAMINE SECRETION IN THE PERFUSED ADRENAL-GLAND(](I) CHANGES ARISING IN INDIVIDUAL GUINEA)

Changes in intracellular free Ca2+ concentration ([Ca2+](i)) arising i n isolated guinea-pig adrenal chromaffin cells stimulated by various r eceptor agonists were analyzed by fura-2 imaging method. Nicotine (10 mu M) and angiotensin II (100 nM; ANG II) induced rises in [Ca2+](i) i n all cells tested. A muscarinic agonist, carbamyl-beta-methylcholine (10 mu M; BCh) and bradykinin (100 nM; BK) elicited [Ca2+](i) rises in 60% and 74% of cells tested, respectively. Cells responsive and nonre sponsive to BCh or BK co-existed even among cells within a cluster, su ggesting that receptors for these agonists may be distributed on indiv idual cells in a considerably inhomogeneous fashion. None of cells sho wed [Ca2+](i) response to histamine (100 mu M). The agonists which ind uced [Ca2+](i) rises consistently evoked catecholamine (CA) secretion from perfused adrenal glands of the guinea-pig. A small transient [Ca2 +](i) rise induced by ANG II, BCh or BK in Ca2+-deficient medium indic ated a release of Ca2+ from intracellular Ca2+ stores. However, a majo r portion of [Ca2+](i) rise induced by these agonists was derived from Ca2+ entry, since a blocker for agonist-mediated Ca2+ entry, -(4-meth oxyphenyl)propoxy]-4-methoxyphenethyl}-1H- imidazole hydrochloride (SK &F 96365) (30 mu M) extensively inhibited both the agonist-induced [Ca 2+](i) rise and CA secretion. The agonist-induced Ca2+ entry consisted in part of Ca2+ influx through voltage-gated Ca2+ channels, which was sensitive to nifedipine.