Activation of G protein by opioid receptors: role of receptor number and G-protein concentration.
The collision-coupling model for receptor-G-protein interaction predicts that the rate of G-protein activation is dependent on receptor density, but not G-protein levels. C6 cells expressing mu- or delta-opioid receptors, or SH-SY5Y cells, were treated with beta-funaltrexamine (mu) or naltrindole-5'-isothiocyanate (delta) to decrease receptor number. The time course of full or partial agonist-stimulated ¿35SGTPgammaS binding did not vary in C6 cell membranes containing <1-25 pmol/mg mu-opioid receptor, or 1. 4-4.3 pmol/mg delta-opioid receptor, or in SHSY5Y cells containing 0. 16-0.39 pmol/mg receptor. The association of ¿35SGTPgammaS binding was faster in membranes from C6mu cells than from C6delta cells. A 10-fold reduction in functional G-protein, following pertussis toxin treatment, lowered the maximal level of ¿35SGTPgammaS binding but not the association rate. These data indicate a compartmentalization of opioid receptors and G protein at the cell membrane.
Remmers
A E
AE
Department of Pharmacology, The University of Michigan Medical School, 1150 W. Medical Center Drive, Ann Arbor, MI 48109-0632, USA.
Clark
M J
MJ
Alt
A
A
Medzihradsky
F
F
Woods
J H
JH
Traynor
J R
JR
D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000032:analysis / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000032:analysis / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000032:analysis / Q000502:physiology*; D014407:Tumor Cells, Cultured
D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019204:GTP-Binding Proteins