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 wa s determined in situ by measuring (CO2)-C-14 release following the hyd roxylation and rapid decarboxylation of C-14-tyrosine offered to the c ells. 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. Tyrosin e 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 w as reduced by 70% by removing extracellular Ca2+ and abolished by remo ving extracellular Ca2+ and chelating intracellular Ca2+ with BAPTA. T yrosine hydroxylase activation by histamine was unaffected by the prot ein kinase C inhibitor Ro 31-8220 but was completely blocked by the pr otein kinase A inhibitor H89. The results indicate that histamine acti vates tyrosine hydroxylase and that this effect is mediated through H- 1 receptors by a mechanism that depends on both extracellular and intr acellular Ca2+ and that requires protein kinase A. (C) 1998 Elsevier S cience B.V. All rights reserved.