Differential antagonism of opioid delta antinociception by [D-Ala2,Leu5,Cys6]enkephalin and naltrindole 5'-isothiocyanate: evidence for delta receptor subtypes.
The present study has investigated the direct opioid delta receptor-mediated antinociception produced by i.c.v. administration of the highly selective delta agonists, [D-Pen2,D-Pen5]enkephalin (DPDPE) and [D-Ala2]deltorphin II, as well as that of the less delta-selective [D-Ser2,Leu5,Thr6]enkephalin (DSLET), by using two novel nonequilibrium opioid antagonists, [D-Ala2,Leu5,Cys6] enkephalin (DALCE) and naltrindole 5'-isothiocyanate (5'-NTII). At times ranging from 8 to 48 hr after a single i.c.v. pretreatment of mice with 5'-NTII, the antinociceptive effects of [D-Ala2] deltorphin II were significantly antagonized. In contrast, 5'-NTII pretreatment at times between 10 min and 24 hr failed to antagonize the antinociceptive effects of DPDPE. Previous studies have shown that pretreatment with i.c.v. DALCE produces a dose- and time-related antagonism of DPDPE, but not morphine, antinociception. However, pretreatment with i.c.v. DALCE failed to antagonize the antinociceptive effects of [D-Ala2]deltorphin II. Similarly, i.c.v. administration of DSLET produced time- and dose-related antinociception which was partially antagonized by either beta-funaltrexamine (beta-FNA) or by ICI 174,864 (N,N-dialyl-Tyr-Aib-Aib-Phe-Leu-OH), suggesting mixed activity at mu and delta receptors. ICI 174,864 produced essentially complete antagonism of DSLET antinociception in beta-FNA-pretreated mice. Pretreatment with 5'-NTII (at -8 to -48 hr), blocked the antinociception produced by DSLET in control or in beta-FNA-pretreated mice. In contrast, pretreatment with DALCE failed to antagonize the antinociception produced by i.c.v. DSLET in either control or in beta-FNA-pretreated mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Jiang
Q
Q
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson.
Takemori
A E
AE
Sultana
M
M
Portoghese
P S
PS
Bowen
W D
WD
Mosberg
H I
HI
Porreca
F
F
D000700:Analgesics / Q000037:antagonists & inhibitors*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D020881:Enkephalin, D-Penicillamine (2,5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D016308:Enkephalin, Leucine-2-Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004745:Enkephalins / Q000037:antagonists & inhibitors; D007276:Injections, Intraventricular; D017879:Isothiocyanates; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009019:Morphinans / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives*; D009292:Narcotic Antagonists; D009842:Oligopeptides / Q000037:antagonists & inhibitors; D011957:Receptors, Opioid / Q000145:classification* / Q000187:drug effects; D017465:Receptors, Opioid, delta; D013861:Thiocyanates / Q000494:pharmacology*
D000700:Analgesics; D004745:Enkephalins; D017879:Isothiocyanates; D009019:Morphinans; D009292:Narcotic Antagonists; D009842:Oligopeptides; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D013861:Thiocyanates; C053821:enkephalin-Leu, Ala(2)-Cys(6)-; C060209:deltorphin II, Ala(2)-; C064283:naltrindole 5'-isothiocyanate; D004743:Enkephalin, Leucine; D009271:Naltrexone; D016308:Enkephalin, Leucine-2-Alanine; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-; D020881:Enkephalin, D-Penicillamine (2,5)-