Potentiation by apamin of histamine-stimulated catecholamine biosynthesis and tyrosine hydroxylase phosphorylation in cultured bovine adrenal chromaffin cells
Kitamura, K.; Houchi, H.; Yoshizumi, M.; Matsumoto, K.; Oka, M.
Tokushima Journal of Experimental Medicine 43(1-2): 17-23
1996
ISSN/ISBN: 0040-8875 PMID: 8885685 Document Number: 457250
The effects of small-conductance Ca-2+-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 Ca-2+. Histamine increased the intracellular free Ca-2+ concentration ((Ca-2+)-i), and this increased (Ca-2+)-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 Ca-2+/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 Ca-2+/calmodulin-dependent protein kinase through an increase in (Ca-2+)-i.