INTERACTION OF [D-PEN(2),D-PEN(5)]ENKEPHALIN AND [D-ALA(2),GLU(4)]DELTORPHIN WITH DELTA-OPIOID RECEPTOR SUBTYPES IN-VIVO

The interaction of [D-Pen(2),D-Pen(5)]enkephalin (DPDPE) and [D-Ala(2),Glu(4)]deltorphin with delta-opioid receptor subtypes was investigated. Pretreatment of mice with the delta(1)-opioid receptor antagonist, [D-Ala(2),Leu(5),Cys(6)]enkephalin (DALCE), produced a virtually complete antagonism of the antinociceptive actions of DPDPE, but had no effect on those of [D-Ala(2),Glu(4)]deltorphin. In DALCE pretreated mice (i.e., delta(1)-opioid receptors blocked), DPDPE was able to significantly antagonize the antinociceptive effects of [D-Ala(2),Glu(4)]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-Ala(2),Glu(4)]deltorphin, but had no effect on the antinociception produced by DPDPE. In 5'-NTII pretreated mice (i.e., delta(2)-opioid receptors blocked), [D-Ala(2),Glu(4)]deltorphin had no effect on the antinociception produced by DPDPE. These data suggest that [D-Ala(2),Glu(4)]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.