Potentiation by apamin of histamine-stimulated catecholamine biosynthesis and tyrosine hydroxylase phosphorylation in cultured bovine adrenal chromaffin cells.
The effects of small-conductance Ca2(+)-activated K+ channel (SK channel) blocker, apamin, on histamine-stimulated catecholamine biosynthesis and tyrosine hydroxylase phosphorylation in cultured bovine adrenal chromaffin cells were investigated. Histamine (10(-10)-10(-6) M) stimulated [14C]catecholamine biosynthesis from [14C]tyrosine (but not from [14C]DOPA). Apamin (10(-6) M) enhanced the histamine-stimulated catecholamine biosynthesis, which was abolished by omission of extracellular Ca2+. Histamine increased the intracellular free Ca2+ concentration ([Ca2+]i), and this increased [Ca2+]i was potentiated by the presence of apamin. The increase in histamine-stimulated catecholamine biosynthesis with apamin was sensitive to the inhibitors of protein kinase C and Ca2+/calmodulin dependent protein kinase. Apamin increased the histamine-induced phosphorylation of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis. These results suggest that in cultured bovine adrenal chromaffin cells the inhibition of SK channel results in potentiation of catecholamine biosynthesis and tyrosine hydroxylase phosphorylation induced by histamine and that these stimulatory effects may result from the activation of protein kinase C and Ca2+/calmodulin-dependent protein kinase through an increase in [Ca2+]i.
Kitamura
K
K
Department of Neurosurgery, School of Medicine, University of Tokushima, Japan.
Houchi
H
H
Yoshizumi
M
M
Matsumoto
K
K
Oka
M
M
D000818:Animals; D001030:Apamin / Q000008:administration & dosage*; D002395:Catecholamines / Q000096:biosynthesis; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism*; D004357:Drug Synergism; D006632:Histamine / Q000008:administration & dosage*; D010766:Phosphorylation; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002395:Catecholamines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin; D006632:Histamine; D014446:Tyrosine 3-Monooxygenase