Summary
The two enantiomers of 3PPP were tested on the spontaneous and electrically-evoked release of 3H-dopamine from slices of the rabbit caudate nucleus and of 3H-acetylcholine (3H-ACh) from slices of the rat caudate nucleus.
In caudate slices labelled with 3H-dopamine, exposure to (+)3PPP (0.1–1 μM) facilitated the spontaneous outflow of radioactivity with a concomitant inhibition of the electrically-evoked release of 3H-dopamine. In the presence of cocaine 10 μM, exposure to (+)3PPP (1 μM) inhibited the electrically evoked release of 3H-dopamine without modifying the spontaneous outflow of radioactivity. This inhibitory effect was not significantly antagonized by S-sulpiride 0.01 μM.
Exposure to (+)3PPP 1 μM inhibited the electrically-evoked release of 3H-ACh, and this effect was not modified by pretreatment with reserpine alone, or in combination with α-methyl-p-tyrosine (α-MT).
In contrast to the (+) enantiomer, exposure to (-)3PPP (0.1–1 μM) facilitated the electrically-evoked release of 3H-dopamine without affecting the spontaneous outflow of radioactivity. (-)3PPP antagonized the inhibitory effect of apomorphine on the electrically-evoked release of 3H-dopamine.
Exposure to (-)3PPP 1 μM did not modify the spontaneous or the electrically-evoked release of 3H-ACh. Yet, this concentration of (-)3PPP antagonized significantly the inhibitory effect of 0.03 μM apomorphine, 1 μM d-amphetamine, and 1 μM (+)3PPP on the electrically-evoked release of 3H-ACh (-)3PPP (0.1–1 μM) was about 100 times less potent than S-sulpiride at antagonizing the inhibitory effect of apomorphine on the electrically-evoked release of 3H-ACh.
It is concluded that under in vitro conditions at the level of the dopamine receptor modulating the release of 3H-ACh from the cholinergic interneuron in the striatum, (+)3PPP behaves as a dopamine receptor agonist while (-)3PPP possesses dopamine receptor-antagonist properties. At the level of the dopaminergic nerve terminal, (-)3PPP facilitates the release of 3H-dopamine probably through the blockade of the dopamine autoreceptors. The dopamine autoreceptor agonists properties of (+)3PPP are difficult to establish in our model because of the dopamine releasing action of this enantiomer.
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Some of the results described in this publication have been presented at the British Pharmacological Society Meeting (Arbilla and Langer 1983).
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Arbilla, S., Langer, S.Z. Differential effects of the stereoisomers of 3PPP in dopaminergic and cholinergic neurotransmission in superfused slices of the corpus striatum. Naunyn-Schmiedeberg's Arch. Pharmacol. 327, 6–13 (1984). https://doi.org/10.1007/BF00504984
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DOI: https://doi.org/10.1007/BF00504984