Spare ligand binding sites in the coupling of opioid receptor to brain GTPase.
Receptor alkylation with 10 microM superfit (SF), an irreversible delta-specific opioid ligand, in rat brain membranes abolished 73% of available binding sites for 3H-DSLET without affecting the stimulation of high affinity GTPase by DSLET. Alkylation with 25 microM SF further decreased the number of low affinity sites and revealed a slight inhibition of GTPase stimulation. Membrane treatment with 75 microM SF abolished high affinity 3H-DSLET binding and reduced GTPase stimulation to below 50% of control accompanied by a 10-fold decrease in the potency of DSLET. Protective alkylation with 25 microM beta-CNA in the presence of DSLET yielded similar results. The findings describe spare delta receptors in their coupling to the GTPase effector component in brain, and reveal possible functional significance of the low affinity ligand binding sites.
Clark
M J
MJ
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109-0010.
Medzihradsky
F
F
D000478:Alkylation; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives*; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta
D008024:Ligands; D009842:Oligopeptides; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D004743:Enkephalin, Leucine; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-; D010744:Phosphoric Monoester Hydrolases; D020558:GTP Phosphohydrolases