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

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