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Effects of dopamine-like drugs on rat striatal adenyl cyclase have implications for CNS dopamine receptor topography

Abstract

THE involvement of central dopaminergic neurones in the pathogenesis of several extrapyramidal movement disorders is well documented1,2. Moreover it has been suggested that dopaminergic mechanisms may also be involved in the physiological mechanisms underlying psychoses3. For these reasons there is considerable neuropharmacological interest in the interaction between anti-Parkinsonian and neuroleptic drugs and central dopaminergic systems. Recently it has been shown that homogenates of tissues containing dopaminergic synapses respond to low concentrations of dopamine by an increased production of cyclic AMP. These areas include the bovine superior cervical ganglion4, the rat and bovine retina5, rat basal ganglia6, olfactory tubercle, nucleus accumbens7 and cortex8. The effects of dopamine in some of these systems are mimicked by dopamine receptor stimulating drugs such as apomorphine6,7 and 1-(3,4-dihydroxybenzyl)-4-(2-pyrimidyl) piperazine (S584)9 and antagonised by neuroleptic drugs6,10–12. It seems, therefore, that these systems represent valid models of CNS dopamine receptors and it has been suggested that they may even comprise the dopamine receptor itself6. We have studied the dopamine-sensitive adenyl cyclase of the rat striatum in order to define some of the structural requirements for dopamine receptor agonists.

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MILLER, R., HORN, A., IVERSEN, L. et al. Effects of dopamine-like drugs on rat striatal adenyl cyclase have implications for CNS dopamine receptor topography. Nature 250, 238–241 (1974). https://doi.org/10.1038/250238a0

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