The activation of tyrosine hydroxylase in noradrenergic neurons during acute nerve stimulation

Tyrosine hydroxylase: a substrate of cyclic AMP-dependent protein kinase.

“…The conversion from curved-line kinetics to straight-line kinetics is compatible with the conversion of Tyr H'ase from a state in which both the less active and more active forms of enzyme, with differing Km values for pterin cofactor, coexist to a state in which the enzyme is almost exclusively in the more active form. Similar kinetics are observed for Tyr H'ase from guinea pig vas deferens (2) and adrenal medulla (6). By using the equations reported for the determination of the relative amounts of two forms of an enzyme with different substrate affinities but similar maximal velocities (6, 28), we estimate that, in the purified preparation (Fig.…”

“…Several investigators, using Tyr H'ase from various tissues, have reported that the enzyme is activated by incubation with adenosine 3',5'-cyclic monophosphate (cAMP)dependent protein kinase, cAMP, ATP, and Mg2+ (2)(3)(4)(5)(6)(7)(8). The enzyme is also activated as a consequence of nerve stimulation, and it has been proposed that the neurally mediated enhancement of enzyme activity (2) results from activation of adenylate cyclase and increased levels of intraneuronal cAMP (3). Because elevations of intracellular cAMP, activation of cAMP-dependent protein kinase, and protein phosphorylation are associated with electrical stimulation or potassium-induced depolarization of brain slices (9), it has been presumed that either Tyr H'ase or an activator of the enzyme is phosphorylated when levels of cAMP are elevated in situ.…”

“…The enzyme was concentrated by ammonium sulfate precipitation (50% saturation, 29.8 g/100 ml). The pellet was resuspended in 0.4 ml of dialysis buffer and dialyzed for 2 (21).…”

Adrenal and vascular tyrosine hydroxylase activity in Goldblatt hypertension.

“…Although the mechanism for increased adrenal TH activity may be different in 1K1C and 2K1C hypertension, the increase in adrenal TH activity may represent a common feature of hypertension. This hypothesis is supported by data demonstrating an increase in the activity of adrenal TH in a variety of the other models of hypertension (e.g., saltsensitive Dahl rat, 49 spontaneously hypertensive rat, 50 -31 mineralocorticoid-salt hypertension, 31 and hypertension produced by section of the aortic and carotid baroreceptor nerves). 52 The ability of many forms of hypertension to develop without the adrenal medulla 53 -57 indicates that the adrenal medulla is not necessary for the development of hypertension; however, it does not preclude a role for the adrenal medulla in the development of the elevated blood pressure in hypertension because of the compensatory influence of other vasopressor systems.…”

Evidence for the involvement of a cyclic AMP-independent protein kinase in the activation of soluble tyrosine hydroxylase from rat striatum.

“…16.2] catalyzes the first and rate-limiting step in the biosynthesis of the neurotransmitter dopamine (1)(2)(3)(4). cAMP and analogs of this cyclic nucleotide are able to increase the activity of the enzyme in crude tissue preparations in the presence of added ATP and Mg2+ (ATP/Mg2+) (5)(6)(7)(8)(9)(10)(11), and this activation is associated with either an increased affinitv of enzyme for cofactor (5,7,11,12) or a reduction of feedback inhibition by dopamine or norepinephrine (7,13). Presumably, cAMP activates cAMP-dependent protein kinase, releasing free catalytic subunit which in turn activates TyrOHase.…”