Faculty Collaboration Database

Interaction between medullary and spinal delta1 and delta2 opioid receptors in the production of antinociception in the rat. J Pharmacol Exp Ther 1999 May;289(2):993-9

Date

04/24/1999

Pubmed ID

10215679

Scopus ID

2-s2.0-0032932714 (requires institutional sign-in at Scopus site)   29 Citations

Abstract

Previous work supports the existence of two types of delta opioid receptor (delta1 and delta2) and a role of both subtypes in the spinal cord and the ventromedial medulla (VMM) in the production of antinociception. Although it is well established that spinal and supraspinal mu opioid receptors interact in a synergistic manner to produce antinociception, little is known about the interaction of delta opioid receptors. This study used isobolographic analysis to determine how delta1 and delta2 opioid receptors in the VMM interact with their respective receptors in the spinal cord to produce antinociception. Concurrent administration of the delta1 opioid receptor agonist [D-Pen2,D-Pen5]enkephalin at spinal and supraspinal sites in a fixed-dose ratio produced antinociception in an additive manner in the tail-flick test. In contrast, concurrent administration of very low doses of the delta2 opioid receptor agonist [D-Ala2,Glu4]deltorphin at spinal and medullary sites produced antinociception in a synergistic manner. However, as the total dose of [D-Ala2,Glu4]deltorphin increased, this interaction converted to additivity. These observations suggest that different mechanisms mediate the antinociceptive effects of different doses of delta2 opioid receptor agonists. The difference in the nature of the interaction produced by delta1 and delta2 opioid receptor agonists provides additional evidence for the existence of different subtypes of the delta opioid receptor. These results also suggest that delta2 opioid receptor agonists capable of crossing the blood-brain barrier will be more potent or efficacious analgesics than delta1 opioid receptor agonists after systemic administration.

Author List

Hurley RW, Grabow TS, Tallarida RJ, Hammond DL

Author

Robert W. Hurley MD, PhD Adjunct Professor of Anesthesiology and CTSI in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Analgesics, Opioid
Animals
Dose-Response Relationship, Drug
Drug Synergism
Enkephalin, D-Penicillamine (2,5)-
Enkephalins
Male
Medulla Oblongata
Microinjections
Oligopeptides
Pain Measurement
Rats
Rats, Sprague-Dawley
Receptors, Opioid, delta
Spinal Cord