Interaction of [-Pen2, -Pen5]enkephalin and [-Ala2, Glu4]deltorphin with [delta]-opioid receptor subtypes in vivo

Abstract

The interaction of [-Pen2, -Pen5]enkephalin (DPDPE) and [-Ala2, Glu4]deltorphin with [delta]-opioid receptor subtypes was investigated. Pretreatment of mice with the [delta]1-opioid receptor antagonists, [-Ala2, Leu5, Cys6]enkephalin (DALCE), produced a virtually complete antagonism of the antinociceptive actions of DPDPE, but had no effect on those of [-Ala2, Glu4]deltorphin. In DALCE pretreated mice (i.e., [delta]1-opioid receptors blocked), DPDPE was able to significantly antagonize the antinociceptive effects of [-Ala2, Glu4]deltorphin. Pretreatment of mice with the [delta]2-opioid receptor antagonist, na naltrindole-5'-isothiocynate (5'-NTII) produced a virtually complete antagonism of the antinociceptive effects of [-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), [-Ala2, Glu4]deltorphin had no effect on the antinociception produced by DPDPE. These data suggest that [-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.