1359107

pubmed:Citation

2

Akin to receptor inactivation with phenoxybenzamine (PBZ) (1 microM, 1 hr), treatment of anterior pituitary cells with 17 beta-estradiol (10 nM, 3 days) right-shifted the dose-response curve for inhibition of prolactin (PRL) secretion by the full agonist R-(-)-N-n-propylnorapomorphine (NPA) and reduced the maximal effect [EC50 (pM) and percent maximal effect: control, 25.4 and 81.2; PBZ, 115.3 and 57.9; 17 beta-estradiol, 358 and 58.6]. PBZ treatment of 17 beta-estradiol-pretreated cultures further reduced the maximal response but did not alter the EC50. Plots of receptor occupancy vs. response indicated a large receptor reserve for NPA (approximately 60%) in control cultures but its abolition by 17 beta-estradiol. 17 beta-Estradiol pretreatment elicited identical rightward shifts (4.5-fold) and similar reductions in maximal PRL inhibition by quinpirole and (+)-3-PPP, although these drugs were partial agonists with dissimilar efficacies relative to NPA (0.61 and 0.12, respectively) at presynaptic striatal D2 receptors. However, receptor inactivation experiments with (+)-3-PPP and quinpirole, and subsequent comparison of receptor occupancy vs. response plots, demonstrated that the relative efficacies of quinpirole and (+)-3-PPP were reversed in the striatum and anterior pituitary. In striatum, half-maximal response to quinpirole and (+)-3-PPP required 6.2 and 30% receptor occupancy, respectively, whereas 25.6 and 9.6% occupancy was required in the pituitary. Pertussis toxin treatment (10 ng/ml, 24 hr) produced large shifts in the dose-response curves for all three agonists (8.4-21.9-fold), but was distinguished from the effects of both PBZ and 17 beta-estradiol by a significant (P < .001) decrease in the slope factor.(ABSTRACT TRUNCATED AT 250 WORDS)

eng

IM

MEDLINE

0022-3565

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NLM

462-9

pubmed-meshheading:1359107-Animals, pubmed-meshheading:1359107-Dopamine Agents, pubmed-meshheading:1359107-Dose-Response Relationship, Drug, pubmed-meshheading:1359107-Ergolines, pubmed-meshheading:1359107-Estradiol, pubmed-meshheading:1359107-GTP-Binding Proteins, pubmed-meshheading:1359107-Male, pubmed-meshheading:1359107-Pertussis Toxin, pubmed-meshheading:1359107-Phenoxybenzamine, pubmed-meshheading:1359107-Piperidines, pubmed-meshheading:1359107-Pituitary Gland, Anterior, pubmed-meshheading:1359107-Prolactin, pubmed-meshheading:1359107-Quinpirole, pubmed-meshheading:1359107-Rats, pubmed-meshheading:1359107-Rats, Sprague-Dawley, pubmed-meshheading:1359107-Receptors, Dopamine D2, pubmed-meshheading:1359107-Receptors, Drug, pubmed-meshheading:1359107-Virulence Factors, Bordetella

Comparative effects of receptor inactivation, 17 beta-estradiol and pertussis toxin on dopaminergic inhibition of prolactin secretion in vitro.

Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.