Differential modulation of mu-opioid receptor signaling to adenylyl cyclase by regulators of G protein signaling proteins 4 or 8 and 7 in permeabilised C6 cells is Gα subtype dependent

摘要: J. Neurochem. (2009) 112, 1026–1034. Abstract Regulators of G protein signaling (RGS) proteins act as GTPase-accelerating to negatively modulate and are defined by a conserved RGS domain with considerable amino acid diversity. To determine the effects specific, purified on mu-opioid signaling, C6 cells stably expressing receptor were rendered permeable treatment digitonin. Mu-opioid inhibition forskolin-stimulated adenylyl cyclase [d-Ala2,N-Me-Phe4,Gly-ol]-enkephalin (DAMGO), mu-specific opioid peptide, remained fully intact in permeabilized cells. Purified RGS4 added resulted twofold loss DAMGO potency but had no effect RGS-insensitive proteins. The inhibitory was reduced same extent RGS8. In contrast, RGS7 inhibited action RGS8 result weak physical association Gαi2 minimal activity cell membranes. These data suggest that differences domains specific contribute differential regulation model is useful for studying aspects protein-coupled signaling.