Summary
Opioid agonists selective for µ-, δ-, and κ-receptors are all capable of regulating the stimulated release of noradrenaline from three terminal fields (cortex, hippocampus, and cerebellum) of the noradrenergic projections from locus coeruleus in the guinea pig brain. Intracerebroventricular injections of pertussis toxin abolished the ability of a µ-selective agonist and of a δ-selective agonist to inhibit stimulated noradrenaline release, but left unaffected the concentration-related inhibition of NE release by a κ agonist. Thus, µ- and δ-receptors have been shown to be coupled to their effector systems in these noradrenergic neurons via guanyl nucleotide binding proteins (G proteins) which are sensitive to pertussis toxin, while κ-receptors in the same neurons appear to be coupled through a different mechanism which is significantly less sensitive to pertussis toxin. In contrast to opioid receptor regulation of noradrenaline release in guinea pig hippocampus, µ-, but not δ- or κ-agonists are capable of regulation of stimulated noradrenaline release from rat hippocampus and cortex, and κ-, but not µ- or δ-agonists are capable of inhibiting the stimulated release of dopamine from rat striatum and cortex. Pertussis toxin injections significantly attenuated µ-agonist inhibition of noradrenaline release, but had no effect on the ability of a κ-selective agonist to regulated dopamine release, confirming the insensitivity of the κ-receptor-effector coupling system to pertussis toxin.
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This work was supported by a grant from the National Institute on Drug Abuse. The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Department of Defense or the Uniformed Services University of the Health Sciences. Animals used in this study were acquired and cared for in accordance with the guidelines published in the NIH Guide for the Care and Use of Laboratory Animals (National Institutes of Health Publications No. 85-23 Revised 1985)
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Werling, L.L., McMahon, P.N. & Cox, B.M. Effects of pertussis toxin on opioid regulation of catecholamine release from rat and guinea pig brain slices. Naunyn-Schmiedeberg's Arch Pharmacol 339, 509–513 (1989). https://doi.org/10.1007/BF00167253
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DOI: https://doi.org/10.1007/BF00167253