title: Interaction of (+)- and (-)-3-PPP with the dopamine receptor in the anterior pituitary gland.
abstract: The interaction of the enantiomers of the novel dopamine agonist, 3-PPP (3-hydroxyphenyl)-N-n-piperidine) with the dopamine receptor in the anterior pituitary gland was examined. Both (+)- and (-)-3-PPP were effective in suppressing the elevation in serum prolactin (PRL) concentrations in rats treated with alpha-methyl-paratyrosine, an inhibitor of dopamine synthesis. The (+)-enantiomer was slightly more potent than the (-)-enantiomer in this regard. In addition, the secretion of PRL from anterior pituitary tissue under in vitro conditions was significantly inhibited by both isomers of 3-PPP, with (+)-3-PPP being approximately 10 times more potent than (-)-3-PPP. Both (+)- and (-)-3-PPP displaced 3H-(-)-N-n-propylnorapomorphine (3H-NPA) and 3H-spiperone from bovine anterior pituitary membranes. The Hill coefficients of (+)- and (-)-3-PPP for the displacement of 3H-spiperone were 0.6 and 0.7, respectively. These results are consistent with the view that the (+)- and (-)-enantiomer exhibit dopamine agonist effects at dopamine receptor sites in the anterior pituitary gland. However, (+)-3-PPP demonstrated marked differences in affinity for 3H-NPA- and 3H-spiperone labeled-sites, whereas (-)-)3-PPP showed the same order of affinity for these two sites. In view of these results and the fact that (-)-3-PPP has also been characterized as a dopamine antagonist at postsynaptic receptor sites in the striatum, (-)-3-PPP might be best described as a partial agonist at pituitary dopamine receptors. Moreover, these data are suggestive of a similarity, at least on a pharmacological basis, between dopamine autoreceptors and dopamine receptors in the anterior pituitary gland.
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000378:metabolism; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D003864:Depression, Chemical; D066298:In Vitro Techniques; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000502:physiology*; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology*; D013134:Spiperone / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D008781:Methyltyrosines; D010880:Piperidines; D011954:Receptors, Dopamine; D013134:Spiperone; C009074:N-n-propylnorapomorphine; D011388:Prolactin; C026539:preclamol; D001058:Apomorphine