Activation of tyrosine hydroxylase by histamine in bovine chromaffin cells

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• 作者：Marley ; Philip D. ; Robotis ; Roula
• 关键词：Histamine ; Chromaffin cells ; Tyrosine hydroxylase ; Calcium ; Protein kinase A ; Protein kinase C
• 刊名：Journal of the Autonomic Nervous System
• 出版年：1998
• 出版时间：May 28, 1998
• 年：1998
• 卷：70
• 期：1-2
• 页码：1-9
• 全文大小：249 K

文摘

Acute activation of tyrosine hydroxylase by histamine has been studied in cultured bovine chromaffin cells. Tyrosine hydroxylase activity was determined in situ by measuring release following the hydroxylation and rapid decarboxylation of -tyrosine offered to the cells. Histamine increased tyrosine hydroxylase activity 2-fold over 10 min with an EC₅₀ of 0.3 μM and maximal response at 10 μM. 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 N^α-methylhistamine and the H₁ agonist 2-thiazolylethylamine, but not by H₂ (dimaprit) or H₃ (R)α-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.