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The protein Ocular albinism 1 is the orphan GPCR GPR 143 and mediates depressor and bradycardic responses to DOPA in the nucleus tractus solitarii
Author(s) -
Hiroshima Y,
Miyamoto H,
Nakamura F,
Masukawa D,
Yamamoto T,
Muraoka H,
Kamiya M,
Yamashita N,
Suzuki T,
Matsuzaki S,
Endo I,
Goshima Y
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12459
Subject(s) - microinjection , solitary nucleus , phenylephrine , endocrinology , receptor , medicine , antagonist , glutamate receptor , solitary tract , chemistry , pharmacology , blood pressure
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.