Phorbol ester stimulates catecholamine synthesis in isolated bovine adrenal medullary cells

Abstract

In isolated bovine adrenal medullary cells, the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA), an activator of protein kinase C, stimulated [¹⁴C]catecholamine synthesis from [¹⁴C]tyrosine, but not from [¹⁴C]DOPA. This stimulatory effect of TPA on [¹⁴C]catecholamine synthesis was not dependent upon extracellular Ca²⁺, and TPA did not affect the uptake of ⁴⁵Ca²⁺ or the release of catecholamine by the cells. TPA also did not affect the intracellular cyclic AMP (cAMP) level. 4α-Phorbol 12,13-didecanoate, which is not an activator of protein kinase C, did not stimulate the synthesis of [¹⁴C]catecholamine from [¹⁴C]tyrosine. The stimulatory effect of TPA on [¹⁴C]catecholamine synthesis was additive with that of carbamylcholine, but not with that of dibutyryl cAMP (DB-cAMP). From these results, it was suggested that protein kinase C is involved in the regulation of tyrosine hydroxylase activity and that this regulatory mechanism might be similar to that involving cAMP.