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Premont J, Thierry AM, Tassin JP, Glowinski J, Blanc G, Bockaert J. 
“Is the Dopamine Sensitive Adenylate Cyclase In The Rat Substantia Nigra Coupled With "Autoreceptors"?”. 
FEBS Letters. 1976;68(1):99-104.
Abstract
INTRODUCTION The neurones, containing dopamine, which originate in the substantia nigra (SN) and project in the striatum constitute the nigro-striatal dopaminergic pathway. The dopamine (DA) released from te dopaminergic nerve terminals interacts with a postsynaptic dopaminergic receptor which is coupled with a specific dopamine sensitive adenylate cyclase [1-6]. This adenylate cyclase has a topographical districution similar to that of dopmaminergic terminals [6,7] and remains after degeneration of the dopaminergic nigro-striatal pathway. From pharmacological data, it has been proposed that dopaminergic terminals in the striatum possesed another category of dopaminergic receptors also called ‘autoreceptors’ [8] since they are sensitive to the neurotransmitter of the neurone on which they are localized. They are involved in the control of dopamine synthesis [8] and release [9,10]. These autoreceptors are widely distributed in all the differenct parts of the dopaminergic neurones and especially on the cell bodies in the substantia nigra [11-14]. The present study was done in order to know if the autoreceptors of the substantia nigra are coupled with an adenylate cyclase in teh same way as the striatal postsynaptic dopaminergic receptors. For this purpose, the substantia nigra was dissected on frozen slices (-7°C) and homogenates prepared: they were found to contain a dopamine sensitive adenylate cyclase. This adenylate cyclase was also stimulated by L-norenpinephrine and to a lesser extent by apomorphine. Various neuroleptics which blocked the stiatal dopamine sensitive adenylate cyclace were also able to inhibit competitively the nigral dopamine sensitive adenylate cyclase. the dopamine sensitive adenylate cyclase was observed to be more concentrated in the pars reticulata ( a region of the substantia nigra rich in dendrites from the dopamine neurones) than in the pars compacta which mainly contains the cell bodies of these neurones and therefore the dopaminergic autoreceptors. In order to check the possibility that the dopamine sensitive adenylate cyclase could be coupled with autoreceptors localized on the dopaminergic neurones, we had specifically destroyed these neurones by a local injection of 6-hydroxydopamine (6-OH-DA). However, after this lesion, the dopamine-sensitive adenylate cyclase of the substantia nigra completely disappeared. These findings can support the hypothesis that the dopamine sensitive adenylate cyclase in the substantia nigra is not coupled with the dopamine autoreceptors. It is proposed that te dopamine sensitive adenylate cyclase described in this report, could be localized on the terminals of the gabaminergic neurones originating within the striatum and/or from the globus pallidus [16,17] and projecting into the substantia nigra.
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