Regulation of retinal dopamine biosynthesis and tyrosine hydroxylase activity by light.
Dopamine (DA)-containing neurons of the rat retina are apparently activated transsynaptically by photic stimulation. Exposure of dark-adapted rats to light increases retinal DA biosynthesis and metabolism. Associated with the light-evoked increase of DA biosynthesis is a rapid activation of tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine biosynthesis. The activation of TH is characterized by an increased affinity of the enzyme for the pteridine cofactor. Because TH in dark-adapted retinas is apparently not saturated with cofactor, the light-evoked increase of affinity is probably responsible for the observed stimulation of DA biosynthesis. Cyclic AMP (cAMP)-dependent protein phosphorylation in vitro activates TH extracted from dark-adapted retinas, and phosphorylation-induced TH activation is very similar and not additive with light-evoked activation of the enzyme. Incubation of viable cell suspensions of dissociated retinas with 8-bromo cAMP also activates TH, which indicates the availability of sufficient cAMP-dependent protein kinase in the proper subcellular compartment to regulate the enzyme in situ. The DA-containing neurons of the rat retina are tonically inhibited in darkness, and evidence is presented that this tonic inhibition involves direct synaptic input to the DA neurons from gamma-aminobutyric acid-containing amacrine cells. The DA-containing neurons are also subject to feedback inhibition through DA receptors, and to modulation by alpha 2-adrenergic receptors.
D000818:Animals; D004298:Dopamine / Q000096:biosynthesis*; D004789:Enzyme Activation; D008027:Light; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D012160:Retina / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000201:enzymology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D005680:gamma-Aminobutyric Acid; D014446:Tyrosine 3-Monooxygenase; D011494:Protein Kinases; D004298:Dopamine