Low-Na+ medium increases the activity and the phosphorylation of tyrosine hydroxylase in the superior cervical ganglion of the rat.
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.
Cahill
A L
AL
Horwitz
J
J
Perlman
R L
RL
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002712:Chlorides / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis; D004987:Ethers / Q000494:pharmacology; D005711:Gallopamil / Q000494:pharmacology; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000201:enzymology*; D015759:Ionomycin; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D002712:Chlorides; D004987:Ethers; D015124:8-Bromo Cyclic Adenosine Monophosphate; D005711:Gallopamil; D013779:Tetrodotoxin; D015759:Ionomycin; D004295:Dihydroxyphenylalanine; D000584:Amiloride; D008094:Lithium; D012964:Sodium; D014446:Tyrosine 3-Monooxygenase; D018021:Lithium Chloride