The participation of cyclic nucleotides and protein kinase in the regulation of norepinephrine synthesis and release during nerve stimulation.
Considerable evidence has accumulated in recent years to suggest that cyclic AMP-dependent protein kinase is responsible for the activation of tyrosine hydroxylase following nerve stimulation. Since stimulation of the central nervous system either by electrical impulses or by exposure of intact brain tissue to depolarizing concentrations of potassium is associated with an activation of adenylate cyclase and an increase in cyclic AMP, it is possible that the normal physiological mechanism by which catecholamine synthesis is enhanced during nerve stimulation involves modification of the enzyme by protein kinase. It has been demonstrated that, in the presence of cyclic AMP, ATP, Mg++ and protein kinase, purified preparations of tyrosine hydroxylase are directly phosphorylated. Since cyclic nucleotides also have been implicated in the process of neurally mediated transmitter release, it is conceivable that activation of adenylate cyclase presynaptically is a common mechanism by which both catecholamine synthesis and norepinephrine release are enhanced during nerve stimulation. Although agonists and antagonists of many putative presynaptic receptors have been found to modulate norepinephrine release during nerve stimulation, no convincing evidence has yet been obtained to suggest that alteration of presynaptic adenylate cyclase activity consequent to nerve stimulation is mediated by a presynaptic action of one or more of these neuromodulators. It is possible that direct depolarization of the nerve terminal in some manner results in activation of presynaptic adenylate cyclase, perhaps by a mechanism involving calcium.
D000818:Animals; D002714:Chlorisondamine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004558:Electric Stimulation; D004789:Enzyme Activation; D006168:Guinea Pigs; D007001:Hypogastric Plexus / Q000502:physiology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D014649:Vas Deferens / Q000201:enzymology / Q000294:innervation*
D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase; D011494:Protein Kinases; D006152:Cyclic GMP; D002714:Chlorisondamine; D009638:Norepinephrine