Activation of Presynaptic Alpha 2-adrenoceptors Attenuates the Inhibitory Effect of Mu-opioid Receptor Agonists on Noradrenaline Release from Brain Slices

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 1986 Aug 1

PMID 3022159

Citations 14

Authors

A N Schoffelmeer

J Putters

A H Mulder

Affiliations

Soon will be listed here.

Abstract

3H-noradrenaline release from rat neocortical slices induced by 15 mM K+ was concentration-dependently inhibited by morphine, [D-Ala2-D-Leu5] enkephalin (DADLE) and the calcium entry blocker Cd2+. Blockade of presynaptic alpha 2-adrenoceptors with phentolamine, almost doubling K+-induced 3H-noradrenaline release, slightly enhanced the relative inhibitory effects of morphine and DADLE, whereas that of Cd2+ remained unaffected. In contrast, activation of presynaptic alpha 2-adrenoceptors with clonidine (1 microM) or TL-99 (1 microM), inhibiting release by about 50%, completely abolished the inhibitory effects of morphine and DADLE without affecting that of Cd2+. When in the presence of 1 microM clonidine adenylate cyclase was activated with forskolin (10 microM), which restored release to the drug-free control level, the opioids still did not display their inhibitory effects. Therefore, mu-opioid receptor efficacy appears to be dependent on the degree of activation of alpha 2-adrenoceptors in central noradrenergic nerve terminals, probably through a local receptor interaction within the nerve terminal membrane.

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