Effects of caffeine on Ca2+ fluxes and secretion in bovine chromaffin cells

The effects of caffeine on Ca²⁺ fluxes and catecholamine secretion in bovine adrenal chromaffin cells were examined. Caffeine inhibited secretion, ⁴⁵Ca²⁺ uptake and cytosolic Ca²⁺ concentration ([Ca²⁺]_i) rise induced by the nicotinic receptor agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP) and the Na⁺ channel activator veratridine. The inhibitory effect of caffeine on high K⁺-induced secretion was smaller than that on DMPP- and veratridine-induced responses. Caffeine only slightly inhibited high K⁺-induced ⁴⁵Ca²⁺ 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 muscarinic and nicotinic receptors as well as at the voltage-dependent Na⁺ channels and to a smaller extent at site(s) distal to Ca²⁺ entry. The effects of caffeine on nicotinic receptors but not on muscarinic receptors can be explained by its ability to raise intracellular cAMP.