Opioid and cannabinoid receptors share a common pool of GTP-binding proteins in cotransfected cells, but not in cells which endogenously coexpress the receptors

Cell Mol Neurobiol. 2000 Jun;20(3):291-304. doi: 10.1023/a:1007058008477.

Abstract

1. Opioid (mu, delta, kappa) and cannabinoid (CB1, CB2) receptors are coupled mainly to Gi/Go GTP-binding proteins. The goal of the present study was to determine whether different subtypes of opioid and cannabinoid receptors, when coexpressed in the same cell, share a common reservoir, or utilize different pools, of G proteins. 2. The stimulation of [35S]GTPgammaS binding by selective opioid and cannabinoid agonists was tested in transiently transfected COS-7 cells, as well as in neuroblastoma cell lines. In COS-7 cells, cotransfection of mu- and delta-opioid receptors led to stimulation of [35S]GTPgammaS binding by either mu-selective (DAMGO) or delta-selective (DPDPE) agonists. The combined effect of the two agonists was similar to the effect of either DAMGO or DPDPE alone, suggesting the activation of a common G-protein reservoir by the two receptor subtypes. 3. The same phenomenon was observed when COS-7 cells were cotransfected with CB1 cannabinoid receptors and either mu- or delta-opioid receptors. 4. On the other hand, in N18TG2 neuroblastoma cells, which endogenously coexpress CB1 and delta-opioid receptors, as well as in SK-N-SH neuroblastoma cells, which coexpress mu- and delta-opioid receptors, the combined effects of the various agonists (the selective cannabinoid DALN and the selective opioids DPDPE and DAMGO) were additive, implying the activation of different pools of G proteins by each receptor subtype. 5. These results suggest a fundamental difference between native and artificially transfected cells regarding the compartmentalization of receptors and GTP-binding proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / pharmacology
  • Analgesics, Opioid / pharmacology
  • Animals
  • COS Cells
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
  • Enkephalin, D-Penicillamine (2,5)- / pharmacology
  • Etorphine / pharmacology
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism*
  • Gene Expression / physiology
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Neuroblastoma
  • Phenanthridines / pharmacology
  • Radioligand Assay
  • Receptors, Cannabinoid
  • Receptors, Drug / genetics*
  • Receptors, Drug / metabolism*
  • Receptors, Opioid / genetics*
  • Receptors, Opioid / metabolism*
  • Receptors, Opioid, delta / genetics
  • Receptors, Opioid, delta / metabolism
  • Receptors, Opioid, kappa / genetics
  • Receptors, Opioid, kappa / metabolism
  • Receptors, Opioid, mu / genetics
  • Receptors, Opioid, mu / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Sulfur Radioisotopes
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Analgesics
  • Analgesics, Opioid
  • Phenanthridines
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Receptors, Opioid
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Sulfur Radioisotopes
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Etorphine
  • desacetylnantradol
  • Enkephalin, D-Penicillamine (2,5)-
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Heterotrimeric GTP-Binding Proteins