JPET Introducing ALZET?ew Model 2006 Pump

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Prather, P. L.
Right arrow Articles by Hales, T. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Prather, P. L.
Right arrow Articles by Hales, T. G.

Vol. 295, Issue 2, 552-562, November 2000

delta -Opioid Receptors Are More Efficiently Coupled to Adenylyl Cyclase Than to L-Type Ca2+ Channels in Transfected Rat Pituitary Cells1

Paul L. Prather, Lei Song, Elemer T. Piros, Ping Y. Law and Tim G. Hales

Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas (P.L.P); Department of Pharmacology, The George Washington University, Washington, DC (L.S., T.G.H.); Department of Physiology, Cornell University, New York, New York (E.T.P.); and Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota (P.Y.L.)

Opioid receptors often couple to multiple effectors within the same cell. To examine potential mechanisms that contribute to the specificity by which delta -receptors couple to distinct intracellular effectors, we stably transfected rat pituitary GH3 cells with cDNAs encoding for delta -opioid receptors. In cells transfected with a relatively low delta -receptor density of 0.55 pmol/mg of protein (GH3DOR), activation of delta -receptors produced inhibition of adenylyl cyclase activity but was unable to alter L-type Ca2+ current. In contrast, activation of delta -receptors in a clone that contained a higher density of delta -receptors (2.45 pmol/mg of protein) and was also coexpressed with µ-opioid receptors (GH3MORDOR), resulted in not only the expected inhibition of adenylyl cyclase activity but also produced inhibition of L-type Ca2+ current. The purpose of the present study was to determine whether these observations resulted from differences in delta -opioid receptor density between clones or interaction between delta - and µ-opioid receptors to allow the activation of different G proteins and signaling to Ca2+ channels. Using the delta -opioid receptor alkylating agent SUPERFIT, reduction of available delta -opioid receptors in GH3MORDOR cells to a density similar to that of delta -opioid receptors in the GH3DOR clone resulted in abolishment of coupling to Ca2+ channels, but not to adenylyl cyclase. Furthermore, although significantly greater amounts of all G proteins were activated by delta -opioid receptors in GH3MORDOR cells, delta -opioid receptor activation in GH3DOR cells resulted in coupling to the identical pattern of G proteins seen in GH3MORDOR cells. These findings suggest that different threshold densities of delta -opioid receptors are required to activate critical amounts of G proteins needed to produce coupling to specific effectors and that delta -opioid receptors couple more efficiently to adenylyl cyclase than to L-type Ca2+ channels.

1 This work was supported in part by National Institute on Drug Abuse Grants DA10936 (to P.L.P.), DA07234-07 (to P.L.P), DA05627-01 (to E.T.P.), DA05010 (to T.G.H.), DA07339 (to P.Y.L.), DA05695 (to P.Y.L.), and an intramural pilot study grant from the University of Arkansas for Medical Sciences (to P.L.P.).

0022-3565/00/2952-0552$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Mol. Pharmacol.Home page
W. Walwyn, N. T. Maidment, M. Sanders, C. J. Evans, B. L. Kieffer, and T. G. Hales
Induction of {delta} Opioid Receptor Function by Up-Regulation of Membrane Receptors in Mouse Primary Afferent Neurons
Mol. Pharmacol., December 1, 2005; 68(6): 1688 - 1698.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
J. L. Shoemaker, B. K. Joseph, M. B. Ruckle, P. R. Mayeux, and P. L. Prather
The Endocannabinoid Noladin Ether Acts as a Full Agonist at Human CB2 Cannabinoid Receptors
J. Pharmacol. Exp. Ther., August 1, 2005; 314(2): 868 - 875.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
A. C. Charles, N. Mostovskaya, K. Asas, C. J. Evans, M. L. Dankovich, and T. G. Hales
Coexpression of delta -Opioid Receptors with {micro} Receptors in GH3 Cells Changes the Functional Response to {micro} Agonists from Inhibitory to Excitatory
Mol. Pharmacol., January 1, 2003; 63(1): 89 - 95.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
J.-G. Liu and P. L. Prather
Chronic Agonist Treatment Converts Antagonists into Inverse Agonists at delta -Opioid Receptors
J. Pharmacol. Exp. Ther., September 1, 2002; 302(3): 1070 - 1079.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
N. A. Martin, M. T. Terruso, and P. L. Prather
Agonist Activity of the delta -Antagonists TIPP and TIPP-psi in Cellular Models Expressing Endogenous or Transfected delta -Opioid Receptors
J. Pharmacol. Exp. Ther., July 1, 2001; 298(1): 240 - 248.
[Abstract] [Full Text]

Home page
 Mol. Pharmacol.Home page
J.-G. Liu and P. L. Prather
Chronic Exposure to {micro}-Opioid Agonists Produces Constitutive Activation of {micro}-Opioid Receptors in Direct Proportion to the Efficacy of the Agonist Used for Pretreatment
Mol. Pharmacol., July 1, 2001; 60(1): 53 - 62.
[Abstract] [Full Text]

Home page
 Mol. Pharmacol.Home page
N. A. Martin and P. L. Prather
Interaction of Co-Expressed {micro}- and {delta}-Opioid Receptors in Transfected Rat Pituitary GH3 Cells
Mol. Pharmacol., April 1, 2001; 59(4): 774 - 783.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
J.-G. Liu, M. B. Ruckle, and P. L. Prather
Constitutively Active {micro}-Opioid Receptors Inhibit Adenylyl Cyclase Activity in Intact Cells and Activate G-proteins Differently than the Agonist [D-Ala2,N-MePhe4,Gly-ol5]Enkephalin
J. Biol. Chem., October 5, 2001; 276(41): 37779 - 37786.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2000 by the American Society for Pharmacology and Experimental Therapeutics.