The protein Ocular albinism 1 is the orphan GPCR GPR 143 and mediates depressor and bradycardic responses to DOPA in the nucleus tractus solitarii

Background and Purpose L ‐ DOPA is generally considered to alleviate the symptoms of P arkinson's disease by its conversion to dopamine. We have proposed that DOPA is itself a neurotransmitter in the CNS. However, specific receptors for DOPA have not been identified. Recently, the gene product of ocular albinism 1 ( OA 1) was found to exhibit DOPA ‐binding activity. Here, we have investigated whether OA 1 is a functional receptor of DOPA in the nucleus tractus solitarii ( NTS ). Experimental Approach We examined immunohistochemical expression of OA 1 in the NTS , and the effects of DOPA microinjected into the depressor sites of NTS on blood pressure and heart rate in anaesthetized rats, with or without prior knock‐down of OA 1 in the NTS, using shRNA against OA 1. Key Results Using a specific OA 1 antibody, OA 1‐positive cells and nerve fibres were found in the depressor sites of the NTS . OA 1 expression in the NTS was markedly suppressed by microinjection into the NTS of adenovirus vectors carrying the relevant shRNA sequences against OA 1. In animals treated with OA 1 shRNA , depressor and bradycardic responses to DOPA, but not those to glutamate, microinjected into the NTS were blocked. Bilateral injections into the NTS of DOPA cyclohexyl ester, a competitive antagonist against OA 1, suppressed phenylephrine‐induced bradycardic responses without affecting blood pressure responses. Conclusion and Implications OA 1 acted as a functional receptor for DOPA in the NTS , mediating depressor and bradycardic responses. Our results add to the evidence for a central neurotransmitter role for DOPA, without conversion to dopamine.