delta-Opioid receptor binding in mouse brain: evidence for heterogeneous binding sites.
In this study we investigated the characteristics of binding sites with which delta opioid receptor agonists interact in homogenates of mouse brain using Krebs-HEPES medium. [3H][D- Ser2,Leu5,Thr6]enkephalin (DSLET), [3H][D-Ala2,D-Leu5]enkephalin (DADLE) and [3H][D-Pen2,D-Pen5]enkephalin (DPDPE) were used to label delta opioid binding sites. The analyses of the saturation binding data of these ligands (Scatchard plots) gave best fits to single rather than multiple site models. The binding capacity (Bmax) labelled by [3H]DSLET was found to be significantly greater than those of [3H]DADLE and [3H]DPDPE in brains of mice. Naltriben (the benzofuran analogue of naltrindole) was equally effective in competing for [3H]DSLET, [3H]DPDPE and [3H]DADLE binding sites. On the other hand, DADLE was significantly more potent in competing for [3H]DADLE and [3H]DPDPE binding sites than for [3H]DSLET binding sites. Also, DPDPE was more potent in competing for the binding sites of [3H]DADLE and [3H]DPDPE than for those of [3H]DSLET. DSLET was found to be equipotent in competing for [3H]DSLET, [3H]DPDPE and [3H]DADLE binding sites. These results suggest a heterogeneity of delta opioid receptors which may be explained possibly by the existence of delta opioid receptor subtypes.
Sofuoglu
M
M
Department of Pharmacology, Medical School, University of Minnesota, Minneapolis 55455.
Portoghese
P S
PS
Takemori
A E
AE
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D020881:Enkephalin, D-Penicillamine (2,5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000378:metabolism; D016308:Enkephalin, Leucine-2-Alanine / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000378:metabolism; D051379:Mice; D009271:Naltrexone / Q000031:analogs & derivatives / Q000378:metabolism; D009292:Narcotic Antagonists / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000378:metabolism*
D004745:Enkephalins; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; C068868:naltrindole benzofuran; D004743:Enkephalin, Leucine; D009271:Naltrexone; D016308:Enkephalin, Leucine-2-Alanine; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-; D020881:Enkephalin, D-Penicillamine (2,5)-