Interaction of [D-Pen2,D-Pen5]enkephalin and [D-Ala2,Glu4]deltorphin with delta-opioid receptor subtypes in vivo.
The interaction of [D-Pen2,D-Pen5]enkephalin (DPDPE) and [D-Ala2,Glu4]deltorphin with delta-opioid receptor subtypes was investigated. Pretreatment of mice with the delta 1-opioid receptor antagonist, [D-Ala2,Leu5,Cys6]enkephalin (DALCE), produced a virtually complete antagonism of the antinociceptive actions of DPDPE, but had no effect on those of [D-Ala2,Glu4]deltorphin. In DALCE pretreated mice (i.e., delta 1-opioid receptors blocked), DPDPE was able to significantly antagonize the antinociceptive effects of [D-Ala2,Glu4]deltorphin. Pretreatment of mice with the delta 2-opioid receptor antagonist, naltrindole-5'-isothiocyanate (5'-NTII) produced a virtually complete antagonism of the antinociceptive effects of [D-Ala2,Glu4]deltorphin, but had no effect on the antinociception produced by DPDPE. In 5'-NTII pretreated mice (i.e., delta 2-opioid receptors blocked), [D-Ala2,Glu4]deltorphin had no effect on the antinociception produced by DPDPE. These data suggest that [D-Ala2,Glu4]deltorphin is highly selective for the delta 2-opioid receptor in vivo, and that neither agonist nor antagonist actions can be demonstrated at delta 1-opioid receptors for this peptide. In contrast, under appropriate conditions, DPDPE can be shown to interact with both delta 1- and delta 2-opioid receptor subtypes; DPDPE may have limited efficacy (i.e., is a partial agonist) at the delta 2-opioid receptor.
Vanderah
T
T
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson 85724.
Takemori
A E
AE
Sultana
M
M
Portoghese
P S
PS
Mosberg
H I
HI
Hruby
V J
VJ
Haaseth
R C
RC
Matsunaga
T O
TO
Porreca
F
F
D000595:Amino Acid Sequence; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D020881:Enkephalin, D-Penicillamine (2,5)-; D016308:Enkephalin, Leucine-2-Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D017879:Isothiocyanates / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009842:Oligopeptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D017465:Receptors, Opioid, delta / Q000187:drug effects*
D000700:Analgesics; D004745:Enkephalins; D017879:Isothiocyanates; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; C053821:enkephalin-Leu, Ala(2)-Cys(6)-; C060209:deltorphin II, Ala(2)-; C064283:naltrindole 5'-isothiocyanate; D009271:Naltrexone; D016308:Enkephalin, Leucine-2-Alanine; D020881:Enkephalin, D-Penicillamine (2,5)-