Stimulation of retinal dopamine biosynthesis in vivo by exogenous tetrahydrobiopterin: relationship to tyrosine hydroxylase activation

Intravitreal injection of tetrahydrobiopterin (BH4), the cofactor for tyrosine hydroxylase (TH), increases 3,4-dihydroxyphenylalanine (DOPA) accumulation in retinas of dark-adapted rats, as does exposure to light. In contrast, BH4 had no significant effect on DOPA accumulation in retinas of light-exposed rats. The levels of endogenous retinal BH4 and the uptake of injected BH4 into the retinal tissue were not affected by light exposure. These data indicate that TH is not saturated with endogenous BH4 in the retinas of dark-adapted rats. In addition, the observations support the interpretation that the decrease in apparent Km of TH for the cofactor in response to light exposure is of sufficient magnitude to allow near saturation of TH by endogenous BH4 and, thus, is causally related to the increase of dopamine biosynthesis in response to short-term photic stimulation.