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 microM 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 microM). 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 microM 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 microM) 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.
Alfinito
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PD
Department of Neurosciences, University of Medicine and Dentistry of New Jersey, Graduate School of Biomedical Sciences, Newark, New Jersey, USA. alfinipe@umdnj.edu
Townes-Anderson
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E
D000557:Ambystoma / Q000378:metabolism*; D000818:Animals; D046508:Culture Techniques; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004298:Dopamine / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008027:Light; D012333:RNA, Messenger / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D050638:Receptors, Dopamine D4; D012160:Retina / Q000378:metabolism / Q000528:radiation effects; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*; D017299:Rod Opsins / Q000235:genetics*; D013997:Time Factors
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D017299:Rod Opsins; D050638:Receptors, Dopamine D4; D017868:Cyclic AMP-Dependent Protein Kinases; D004298:Dopamine