Dopamine D₄ receptor-mediated regulation of rod opsin mRNA expression in tiger salamander

Light stimulates dopamine release in the retina and has been shown to rapidly up-regulate rod opsin mRNA. In the present study, we tested the effect of dopamine on rod opsin mRNA expression and examined the hypothesis that dopamine can mediate a light-evoked increase in opsin gene expression. Northern blots showed that a 30-min light-exposure increased rod opsin mRNA expression 27%. In situ hybridization on isolated rods showed that 500 nM dopamine and 1 μM quinpirole (dopamine D₂/D₃/D₄ agonist) increased opsin mRNA 45% and 26%, respectively. The effect of quinpirole was selectively blocked by the D₄ antagonist, L750,667 (20 μM). In very low density cultures, quinpirole increased opsin expression 46%, suggesting a direct effect on rod photoreceptors. Consistent with a dopamine D₄ receptor mechanism, 1 μM H-89 (protein kinase A inhibitor) increased opsin mRNA 39%. Finally, intravitreal injection of quinpirole increased opsin mRNA 21% whereas injection of L750,667 (10 μM) blocked the light-evoked increase in opsin expression. These data show that rod opsin mRNA is up-regulated by dopamine binding a D₄-like receptor on rods, possibly through inhibition of protein kinase A, and that endogenous dopamine can mediate the light-evoked increase in opsin mRNA expression.