Regulation of the phosphorylation state of rhodopsin by dopamine

G protein-coupled receptors (GPCRs) are regulated by kinases and phosphatases that control their phosphorylation state. Here, the possibility that the state of GPCR phosphorylation could be affected by paracrine input was explored. We show that dopamine increased the rate of dephosphorylation of rhodopsin, the light receptor, in intact frog retinas. Further, we found that rod outer segments from dopamine-treated retinas contained increased rhodopsin phosphatase activity, indicating that this effect of dopamine on rhodopsin was mediated by stimulation of rhodopsin phosphatase. Dopamine is a ubiquitous neuromodulator and, in the retina, is released from the inner cell layers. Thus, our results identify a pathway for feedback regulation of rhodopsin from the inner retina and illustrate the involvement of dopamine in paracrine regulation of the sensitivity of a GPCR.