Interaction between medullary and spinal delta1 and delta2 opioid receptors in the production of antinociception in the rat

Robert W Hurley; Theodore S Grabow; Ronald J Tallarida; Donna L Hammond

doi:10.1016/S0022-3565(24)38227-8

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Interaction between medullary and spinal delta1 and delta2 opioid receptors in the production of antinociception in the rat

Journal article

Peer reviewed

Interaction between medullary and spinal delta1 and delta2 opioid receptors in the production of antinociception in the rat

Robert W Hurley, Theodore S Grabow, Ronald J Tallarida and Donna L Hammond

The Journal of pharmacology and experimental therapeutics, Vol.289(2), pp.993-999

05/1999

DOI: 10.1016/S0022-3565(24)38227-8

PMID: 10215679

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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.

Receptors, Opioid, delta - metabolism

Spinal Cord - drug effects

Spinal Cord - metabolism

Microinjections

Medulla Oblongata - drug effects

Medulla Oblongata - anatomy & histology

Medulla Oblongata - metabolism

Analgesics, Opioid - pharmacology

Rats

Male

Pain Measurement - drug effects

Spinal Cord - anatomy & histology

Receptors, Opioid, delta - drug effects

Rats, Sprague-Dawley

Enkephalin, D-Penicillamine (2,5)

Dose-Response Relationship, Drug

Drug Synergism

Animals

Enkephalins - pharmacology

Oligopeptides - pharmacology

Details

Title: Subtitle: Interaction between medullary and spinal delta1 and delta2 opioid receptors in the production of antinociception in the rat
Creators: Robert W Hurley - Committee on Neurobiology, University of Chicago, Chicago, Illinois, USA
Theodore S Grabow
Ronald J Tallarida
Donna L Hammond
Resource Type: Journal article
Publication Details: The Journal of pharmacology and experimental therapeutics, Vol.289(2), pp.993-999
Publisher: United States
DOI: 10.1016/S0022-3565(24)38227-8
PMID: 10215679
ISSN: 0022-3565
eISSN: 1521-0103
Grant note: R01-DA06736 / NIDA NIH HHS T32-HD07009 / NICHD NIH HHS F30-DA05784 / NIDA NIH HHS
Language: English
Date published: 05/1999
Academic Unit: Iowa Neuroscience Institute; Nursing; Anesthesia; Neuroscience and Pharmacology
Record Identifier: 9984007192402771

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