Evidence for delta opioid receptor subtypes in rat spinal cord: studies with intrathecal naltriben, cyclic[D-Pen2, D-Pen5] enkephalin and [D-Ala2, Glu4]deltorphin.
This study characterized the antinociception produced by intrathecal (i.t.) administration of the respective delta-2 and delta-1 receptor-selective agonists, [D-Ala2, Glu4]deltorphin (DELT) and DPDPE or the mu receptor selective agonist DAMGO in the rat. It also determined whether the antinociception produced by these opioid agonists was differentially affected by i.t. coadministration of the delta-2 receptor-selective antagonist, naltriben (NTB). In the tail-flick test, the ED50 values of DELT and DPDPE were 2.7 micrograms (3.4 nmol) and 19.0 micrograms (29.4 nmol), respectively. Coadministration of 3 micrograms (6.4 nmol) of NTB increased the ED50 of DELT at least 25-fold, but did not significantly increase the ED50 of DPDPE. These findings suggest that: 1) DELT and DPDPE act at different delta opioid receptor subtypes in the rat spinal cord; 2) 3 micrograms of NTB can distinguish these receptor subtypes and 3) activation of either delta-1 or delta-2 receptors is sufficient to produce antinociception in the tail-flick test. Although NTB did not antagonize the increase in tail-flick latency produced by 0.1 to 0.3 microgram of DAMGO, it did antagonize the increase produced by 0.03 microgram of DAMGO resulting in a steeper dose-response relationship. Unlike DPDPE or DAMGO, DELT did not increase hot-plate latency except at a dose that produced adverse motor effects. Coadministration of 3 micrograms of NTB antagonized the increase in hot-plate latency produced by DPDPE, but not DAMGO, suggesting that this delta-1 receptor-selective agonist may also have efficacy at delta-2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Stewart
P E
PE
Department of Anesthesia and Critical Care, University of Chicago, Illinois.
Hammond
D L
DL
D000818:Animals; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000187:drug effects; D012018:Reflex / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects*
D004745:Enkephalins; D009292:Narcotic Antagonists; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C068868:naltrindole benzofuran; C059567:deltorphin; D009271:Naltrexone; D020881:Enkephalin, D-Penicillamine (2,5)-