Activation of tyrosine hydroxylase by histamine in bovine chromaffin cells

Acute activation of tyrosine hydroxylase by histamine has been studied in cultured bovine chromaffin cells. Tyrosine hydroxylase activity was determined in situ by measuring (CO2)-C-14 release following the hydroxylation and rapid decarboxylation of C-14-tyrosine offered to the cells. Histamine increased tyrosine hydroxylase activity 2-fold over 10 min with an EC50 of 0.3 mu M and maximal response at 10 mu M. Tyrosine hydroxylase activation was detectable within 1-2 min and maintained for at least 10 min. The effect of histamine was fully blocked by the H-1 antagonist mepyramine, but unaffected by H-2 (cimetidine) and H-3 (thioperamide) antagonists. It was mimicked by N-alpha-methylhistamine and the H-1 agonist 2-thiazolylethylamine, but not by H-2 (dimaprit) or H-3 (R)alpha-methylhistamine) agonists. The response to histamine was reduced by 70% by removing extracellular Ca2+ and abolished by removing extracellular Ca2+ and chelating intracellular Ca2+ with BAPTA. Tyrosine hydroxylase activation by histamine was unaffected by the protein kinase C inhibitor Ro 31-8220 but was completely blocked by the protein kinase A inhibitor H89. The results indicate that histamine activates tyrosine hydroxylase and that this effect is mediated through H-1 receptors by a mechanism that depends on both extracellular and intracellular Ca2+ and that requires protein kinase A. (C) 1998 Elsevier Science B.V. All rights reserved.