Low-Na+ medium increases the activity and the phosphorylation of tyrosine hydroxylase in the superior cervical ganglion of the rat.
کلید واژه ها
خلاصه
Incubation of the rat superior cervical ganglion in Na+-free or low-Na+ medium increased the rate of synthesis of 3,4-dihydroxyphenylalanine (DOPA) in the ganglion fourfold and caused a concomitant stable activation of tyrosine hydroxylase. DOPA synthesis was half-maximal in medium containing about 20 mM Na+. Low-Na+ medium also increased the incorporation of 32Pi into tyrosine hydroxylase; the dependence of tyrosine hydroxylase phosphorylation on the Na+ concentration resembled that of DOPA synthesis. The stimulatory effects of low-Na+ medium on DOPA production and on tyrosine hydroxylase activity in vitro were dependent on extra-cellular Ca2+. The stimulation of DOPA synthesis in low-Na+ medium was inhibited by methoxyverapamil, an inhibitor of Ca2+ uptake, and was partially blocked by tetrodotoxin, but it was not affected by the cholinergic antagonists hexamethonium and atropine. Ionomycin, a calcium ionophore, stimulated DOPA synthesis to about the same extent as low-Na+ medium and also increased the incorporation of 32Pi into tyrosine hydroxylase. 8-Bromo cyclic AMP (1 mM) also stimulated DOPA production in the ganglion, and this stimulation was more than additive with that produced by low-Na+ medium. These data support the hypothesis that low-Na+ medium stimulates DOPA synthesis by raising intracellular Ca2+, which then promotes the phosphorylation of tyrosine hydroxylase.