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Further functional in vitro comparison of pre- and postsynaptic dopamine receptors in the rabbit caudate nucleus

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Summary

Slices of the rabbit caudate nucleus were preincubated with 3H-dopamine or 3H-choline and then superfused and stimulated electrically. DiPr-5,6-ADTN reduced the stimulation-evoked overflow of tritium over the same concentration range, independently of whether slices had been preincubated with 3H-dopamine or 3H-choline, and the same was true for apomorphine, NPA and pergolide. Three other putative dopamine receptor agonists, namely 3-PPP, DPI and SKF 38393, failed to decrease the evoked overflow of tritium. Each of six antagonists — (−)-sulpiride, (+)-sulpiride, CGP 11109 A, cis-flupentixol, domperidone and corynanthine —increased the evoked overflow over the same concentration range in experiments with 3H-dopamine and in those with 3H-choline. For each of these antagonists except cis-flupentixol, and also for chlorpromazine, haloperidol and rauwolscine, the pA2 values against apomorphine obtained in 3H-dopamine and in 3H-choline experiments were closely similar. The antagonist effect of cis-flupentixol against apomorphine was not purely competitive. (−)-Sulpiride was a more potent antagonist than (+)-sulpiride, and cis-flupentixol was more potent than trans-flupentixol.

This study supplements a previous one in which (±)-sulpiride, metoclopramide and molindone were used as antagonists. It is a functional in vitro approach to receptor characterization, as opposed to radioligand binding studies or in vivo investigations. The results show that a large number of dopamine receptor agonists and antagonists are unable to distinguish between the presynaptic, release-inhibiting dopamine autoreceptors and those postsynaptic dopamine receptors which, when activated, depress the release of acetylcholine. Both receptors can be classified as D2. There was an excellent correlation between pA2 values and the — log K i values of antagonists, taken from the literature, for inhibition of the binding of 3H-spiperone to rat striatal membrane fragments. The correlation supports the view that the sites labelled by 3H-spiperone are true receptors, although the affinities in the binding experiments were consistently lower than the functionally determined affinities in the intact tissue.

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Abbreviations

CGP 11109 A:

N-[(1-ethyl-2-pyrrolidinyl)methyl]-2,6-dimethoxy-nicotinamide

DiPr-5,6-ADTN:

2-(N,N-di-n-propyl) amino-5,6-dihydroxy-1,2,3,4-tetrahydronaphthalene

DPI:

(3,4-dihydroxyphenylimino)-2-imidazolidine

NPA:

N-n-propyl-norapomorphine

3-PPP:

3-(3-hydroxyphenyl)-N-n-propyl-piperidine

SKF 38393:

2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine

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Starke, K., Späth, L., Lang, J.D. et al. Further functional in vitro comparison of pre- and postsynaptic dopamine receptors in the rabbit caudate nucleus. Naunyn-Schmiedeberg's Arch. Pharmacol. 323, 298–306 (1983). https://doi.org/10.1007/BF00512467

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