Using approaches emphasizing differential antagonism of receptor selective agonists and cross-tolerance paradigms, evidence in vivo has suggested the existence of subtypes of opioid δ receptors, which have been termed δ1 and δ2. Recent work has elucidated the structure of an opioid δ receptor. The present investigation attempted to continue to test the hypothesis of subtypes of 5 receptors and to correlate the cloned δ receptor with the existing pharmacological classification. Synthetic oligodeoxynucleotides (oligos) complementary to the 5' end of the cloned δ receptor coding region (antisense) or its corresponding sequence (sense) were given by intracerebroventricular (i.c.v.) administration to mice, twice-daily for 3 days and antinociceptive responses to selective agonists at putative δ1 and δ2 receptors were subsequently determined. Treatment with antisense, but not sense, oligo significantly inhibited the response to [D-Ala2, GIu4]deItorphin (δ2 agonist), but not to [D-Pen2, D-Pen5]enkephalin (DPDPE, δ1 agonist). Further, subsequent administration of DPDPE elicited a full antinociceptive response in the same anti-sense oligo treated mice which did not show a significant response to [D-Ala2, Glu4]deltorphin while antisense oligo treated mice which responded to DPDPE did not show antinociception when tested subsequently with [D-Ala2, Glu4]deItorphin. The data suggest that the cloned δ receptor corresponds to that pharmacologically classified as δ2 and continue to support the concept of subtypes of opioid δ receptors.
- Antisense oligodeoxynucleotides
- DPDPE, [D-Ala, Glu]deltorphin
- Opioid δ receptor subtypes
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