Different contributions of voltage-sensitive Ca2+ channels to histamine-induced catecholamine release and tyrosine hydroxylase activation in bovine adrenal chromaffin cells

Histamine stimulates catecholamine release and tyrosine hydroxylase activit y in a Ca2+-dependent manner in bovine adrenal chromaffin cells. The role o f voltage-sensitive Ca2+ channels in these two responses has been investiga ted. Using an EC50 concentration of histamine, 1 mu M, catecholamine releas e was enhanced by (+/-)BayK8644, and partially inhibited by nitrendipine an d omega-agatoxin IVA, blockers of L-and P/Q-type Ca2+ channels, omega-Conot oxin GVIA gave small and variable inhibitory effects. With a maximal histam ine concentration, 10 mu M, similar results were obtained except that now o mega-conotoxin GVIA reliably reduced release. In contrast, neither (+/-)Bay K8644 nor any of the individual Ca2+ channel antagonists had any significan t effect on tyrosine hydroxylase (TOH) activation induced by either an EC,, or a maximal concentration of histamine. When high concentrations of nitre ndipine, omega-conotoxin GVIA and omega-agatoxin IVA were combined with ome ga-conotoxin MVIIC (a non-selective blocker of N, P and Q channels) to bloc k voltage-sensitive Ca2+ channels in these cells, release induced by K+ dep olarization was completely blocked. Release caused by histamine, however, w as substantially reduced but not abolished. The combination of antagonists also only partially inhibited TOH activation by histamine. The results show that the G protein-coupled receptor agonist histamine activates several di fferent types of voltage-sensitive Ca2+ channels in chromaffin cells to med iate its cellular effects. Histamine may also activate additional pathways for Ca2+ entry. The results also suggest that the manner by which Ca2+ cont rols release and TOH activation once it has entered chromaffin cells throug h these channels are different.