The protein Ocular albinism 1 is the orphan GPCR GPR143 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 Parkinson'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 (OA1) was found to exhibit DOPA-binding activity. Here, we have investigated whether OA1 is a functional receptor of DOPA in the nucleus tractus solitarii (NTS).


EXPERIMENTAL APPROACH
We examined immunohistochemical expression of OA1 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 OA1 in the NTS, using shRNA against OA1.


KEY RESULTS
Using a specific OA1 antibody, OA1-positive cells and nerve fibres were found in the depressor sites of the NTS. OA1 expression in the NTS was markedly suppressed by microinjection into the NTS of adenovirus vectors carrying the relevant shRNA sequences against OA1. In animals treated with OA1 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 OA1, suppressed phenylephrine-induced bradycardic responses without affecting blood pressure responses.


CONCLUSION AND IMPLICATIONS
OA1 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.
['Hiroshima|Y|Y|', 'Miyamoto|H|H|', 'Nakamura|F|F|', 'Masukawa|D|D|', 'Yamamoto|T|T|', 'Muraoka|H|H|', 'Kamiya|M|M|', 'Yamashita|N|N|', 'Suzuki|T|T|', 'Matsuzaki|S|S|', 'Endo|I|I|', 'Goshima|Y|Y|']
D000818:Animals D015153:Blotting, Western D001919:Bradycardia D016466:CHO Cells D019556:COS Cells D002522:Chlorocebus aethiops D006224:Cricetinae D003412:Cricetulus D000229:Dependovirus D004295:Dihydroxyphenylalanine D015259:Dopamine Agents D018014:Gene Transfer Techniques D006339:Heart Rate D007031:Hypothalamus D007150:Immunohistochemistry D008297:Male D010957:Plasmids D051381:Rats D017208:Rats, Wistar D060888:Real-Time Polymerase Chain Reaction D043562:Receptors, G-Protein-Coupled D017552:Solitary Nucleus
nucleus tractus solitarii neurotransmitter 4-dihydroxyphenylalanine G-protein coupled receptor L-3 baroreceptor reflex