Interaction of (+)- and (-)-3-PPP with the dopamine receptor in the anterior pituitary gland

M. Mikuni*, G. A. Gudelsky, M. Simonovic, H. Y. Meltzer

*Corresponding author for this work

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The interaction of the enantiomers of the novel dopamine agonist, 3-PPP (3-(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 α-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.

Original languageEnglish (US)
Pages (from-to)239-246
Number of pages8
JournalLife Sciences
Volume34
Issue number3
DOIs
StatePublished - Jan 16 1984

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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