EFFECTS OF CAFFEINE ON CA2+ FLUXES AND SECRETION IN BOVINE CHROMAFFINCELLS

The effects of caffeine on Ca2+ fluxes and catecholamine secretion in bovine adrenal chromaffin cells were examined. Caffeine inhibited secr etion, Ca-45(2+) uptake and cytosolic Ca2+ concentration([Ca2+](i)) ri se induced by the nicotinic receptor agonist 1,1-dimethyl-4-phenylpipe razinium (DMPP) and the Na+ channel activator veratridine. The inhibit ory effect of caffeine on high K+-induced secretion was smaller than t hat on DMPP- and veratridine-induced responses. Caffeine only slightly inhibited high K+-induced Ca-45(2+) uptake and did not affect [Ca2+]( i) rise. Caffeine also inhibited muscarinic receptor-mediated inositol phosphate generation. Our results suggest that the inhibitory effects of caffeine on bovine chromaffin cells mainly occur at both muscarini c and nicotinic receptors as well as at the voltage-dependent Na+ chan nels and to a smaller extent at site(s) distal to Ca2+ entry. The effe cts of caffeine on nicotinic receptors but not on muscarinic receptors can be explained by its ability to raise intracellular cAMP.