Agonist and antagonist effects of 3-PPP enantiomers on functional dopamine autoreceptors and postsynaptic dopamine receptors in vitro

In contrast to racemic 3-PPP (3-(3-hydroxyphenyl)-N-n-propylpiperidine), (+)-3-PPP appeared to inhibit the electrically evoked release of both [3H]dopamine (DA) and [14C]acetylcholine (ACh) from superfused rat neostriatal slices, although it was considerably less potent in this respect that the DA receptor agonists apomorphine, TL-99 (6,7-dihydroxy-N,N-dimethyl-2-aminotetralin) and LY 141865. At concentrations higher than 1 microM both of the 3-PPP enantiomers increased the spontaneous efflux of 3H but not that of 14C. (+)3-PPP also inhibited the cholera toxin-stimulated release of immunoreactive alpha-MSH from dispersed intermediate lobe cells of the rat pituitary gland. The inhibitory effects of (+)3-PPP on both transmitter and alpha-MSH release were antagonized by the selective D-2 receptor antagonist (-)-sulpiride. Neither [3H]DA nor [14C]ACh release were inhibited by (-)3-PPP but, in contrast, the release-inhibiting effect of the selective D-2 receptor agonist LY 141865 as well as that of (+)3-PPP were antagonized by (-)3-PPP, although less effectively than by (-)sulpiride. The inhibitory effect of LY 141865 on alpha-MSH release from intermediate lobe cells was also antagonized by (-)3-PPP. The data indicate that (+)3-PPP is a weak agonist and (-)3-PPP a weak antagonist at D-2 receptors and that neither of the 3-PPP enantiomers interacts selectively with DA autoreceptors mediating presynaptic modulation of striatal DA release.