![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
E Meller, T Puza, J Diamond, HD Lieu and K Bohmaker
Millhauser Laboratories, Department of Psychiatry, New York University School of Medicine, New York.
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)
This article has been cited by other articles:
|
|
 |
|
  P. R. Moya, K. A. Berg, M. A. Gutierrez-Hernandez, P. Saez-Briones, M. Reyes-Parada, B. K. Cassels, and W. P. Clarke Functional Selectivity of Hallucinogenic Phenethylamine and Phenylisopropylamine Derivatives at Human 5-Hydroxytryptamine (5-HT)2A and 5-HT2C Receptors J. Pharmacol. Exp. Ther., June 1, 2007; 321(3): 1054 - 1061. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Maudsley, B. Martin, and L. M. Luttrell The Origins of Diversity and Specificity in G Protein-Coupled Receptor Signaling J. Pharmacol. Exp. Ther., August 1, 2005; 314(2): 485 - 494. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Christopoulos and T. Kenakin G Protein-Coupled Receptor Allosterism and Complexing Pharmacol. Rev., June 1, 2002; 54(2): 323 - 374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Waelbroeck Activation of Guanosine 5'-[{gamma}-35S]thio-triphosphate Binding through M1 Muscarinic Receptors in Transfected Chinese Hamster Ovary Cell Membranes: 2. Testing the "Two-States" Model of Receptor Activation Mol. Pharmacol., April 1, 2001; 59(4): 886 - 893. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. KENAKIN Inverse, protean, and ligand-selective agonism: matters of receptor conformation FASEB J, March 1, 2001; 15(3): 598 - 611. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Freeman, B. Kanyicska, A. Lerant, and G. Nagy Prolactin: Structure, Function, and Regulation of Secretion Physiol Rev, October 1, 2000; 80(4): 1523 - 1631. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Cordeaux, S. A. Nickolls, L. A. Flood, S. G. Graber, and P. G. Strange Agonist Regulation of D2 Dopamine Receptor/G Protein Interaction. EVIDENCE FOR AGONIST SELECTION OF G PROTEIN SUBTYPE J. Biol. Chem., July 27, 2001; 276(31): 28667 - 28675. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
