NDLI: Go mediates the coupling of the mu opioid receptor to adenylyl cyclase in cloned neural cells and brain.

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Go mediates the coupling of the mu opioid receptor to adenylyl cyclase in cloned neural cells and brain.

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Go mediates the coupling of the mu opioid receptor to adenylyl cyclase in cloned neural cells and brain.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Carter, B. D. Medzihradsky, F.
Description	Author Affiliation: Carter BD ( Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109-0606.);
Abstract	In membranes from SH-SY5Y human neuroblastoma cells differentiated with retinoic acid, the mu-selective agonist Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol (DAMGO) inhibited cAMP formation with an IC50 of 26 nM. Two separate antibodies raised against distinct regions of the Go alpha sequence attenuated the effect of DAMGO by 50-60%, whereas antibodies to Gi alpha 1,2 or Gi alpha 3 reduced the mu-opioid signal insignificantly or to a lesser extent. In contrast, inhibition of adenylyl cyclase by the delta-opioid agonist Tyr-D-Pen-Gly-Phe-D-Pen-OH (DPDPE; Pen = penicillamine) was very sensitive to the Gi alpha 1,2 antibody. In membranes from rat brain striatum, coupling of the mu opioid receptor to adenylyl cyclase was also maximally blocked by antibodies to Go alpha. After long-term treatment of the cells with DAMGO, the content of Go alpha was reduced by 26%, whereas the levels of Gi alpha 1,2, Gi alpha 3, and Gs alpha were unaltered. Addition of Go, purified from bovine brain, to membranes from pertussis toxin-treated SH-SY5Y cells restored the inhibition of adenylyl cyclase by DAMGO to 70% of that in toxin-untreated cells. To comparably restore the effect of DPDPE, much higher concentrations of Go were required. By demonstrating mediation of cAMP-dependent signal transduction by Go, these results describe (i) an additional role for this G protein present at a high concentration in brain, (ii) preferential, although not exclusive, interaction of mu and delta opioid receptors with different G protein subtypes in coupling to adenylyl cyclase, and (iii) reduced levels of Go following chronic opioid treatment of SH-SY5Y cells with mu opioids.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	9
Volume Number	90
Language	English
Publisher	National Academy of Sciences
Publisher Date	1993-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Adenylate Cyclase Metabolism Analgesics Pharmacology Corpus Striatum Enkephalins GTP-Binding Proteins Neuroblastoma Receptors, Opioid, Mu Adenylate Cyclase Toxin Animals Antibodies Cell Membrane Drug Effects Enzymology Clone Cells Cyclic AMP Enkephalin, Ala(2)-MePhe(4)-Gly(5)- Enkephalin, D-Penicillamine (2,5)- Immunology Kinetics Membrane Proteins Isolation & Purification Pertussis Toxin Somatostatin Analogs & Derivatives Tumor Cells, Cultured Virulence Factors, Bordetella Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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