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 14CO2 release following the hydroxylation and rapid decarboxylation of 14C-tyrosine offered to the cells. Histamine increased tyrosine hydroxylase activity 2-fold over 10 min with an EC50 of 0.3 microM and maximal response at 10 microM. 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 H1 antagonist mepyramine, but unaffected by H2 (cimetidine) and H3 (thioperamide) antagonists. It was mimicked by Nalpha-methylhistamine and the H1 agonist 2-thiazolylethylamine, but not by H2 (dimaprit) or H3 (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 H1 receptors by a mechanism that depends on both extracellular and intracellular Ca2+ and that requires protein kinase A.
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia. p.marley@unimelb.edu.au
P D
PD
Marley
R
R
Robotis
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002417:Cattle; D002614:Chelating Agents / Q000494:pharmacology; D019439:Chromaffin Cells / Q000187:drug effects / Q000201:enzymology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D002614:Chelating Agents; D004791:Enzyme Inhibitors; D017442:Histamine Agonists; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D006632:Histamine; D014446:Tyrosine 3-Monooxygenase; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D002118:Calcium