Sustained Phosphorylation of Tyrosine Hydroxylase at Serine 40 in VIVO

Sustained Phosphorylation of Tyrosine Hydroxylase at Serine 40 in VIVO

Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine synthesis. Its activity is know to be controlled acutely (minutes) by phosphorylation and chronically (days) by protein synthesis. Using bovine adrenal chromaffin cells our laboratory found that nicotine and PACAP, the major neurotransmitters released on activation of splanchnic nerves, induced sustained activation of TH (via Ser40 phosphorylation) for 24 h, which was completely independent of TH protein synthesis. Glucoprivation elicited by 2-deoxyglucose (2DG) which is a metabolic stressor known to activate the adrenal chromaffin cells by splanchic nerve activation did not show sustained TH phosphorylation. TH protein levels were significantly increased (2.3 fold, p < 0.001) but Ser40 phosphorylation levels at 24 h were not increased. However another stressor, neonatal injection of lipopolysaccharide (LPS) did cause a sustained increase in Ser40 phosphorylation levels at 4 h and 24 h following injection (F(1,21) = 6.19, p < 0.05). In this case TH protein levels were not significantly altered. This is the first study to our knowledge to identify sustained Ser40 phosphorylation in vivo. Sustained Ser40 phosphorylation has
the ability to cause sustained TH activation and sustained catecholamine synthesis without the need for TH protein synthesis. It represents a novel phase between acute and chronic maintenance of catecholamine synthesis.

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