Mu- and delta-opioid receptors inhibitorily linked to dopamine-sensitive adenylate cyclase in rat striatum display a selectivity profile toward endogenous opioid peptides different from that of presynaptic mu, delta and kappa receptors

A. N M Schoffelmeer*, T. J. De Vries, F. Hogenboom, A. H. Mulder

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The apparent affinities of endogenous opioid peptides for non- competitively interacting mu and delta receptors, inhibitorily linked to dopamine (DA) D-1 receptor-stimulated adenylate cyclase, were investigated in superfused rat striatal slices exposed to 40 μM DA in the presence of 10 μM of the selective D-2 receptor antagonist (-)sulpiride. In the presence of peptidase inhibitors, a comparison was made with the apparent affinities of opioid peptides toward independent presynaptic opioid receptors in brain slices. β-Endorphin1-31 had an about 100-fold higher apparent affinity (EC50: 1 nM) toward presynaptic mu-opioid receptors, mediating inhibition of the electrically evoked neocortical [3H]norepinephrine release, than for the striatal adenylate cyclase-coupled mu·receptors. In contrast, the kappa- opioid receptor agonist dynorphin A1-13 displayed a similar apparent affinity (EC50: 0.1 μM) toward these functionally different mu receptors. Both Leu- and Met-enkephalin showed only a 3-fold higher apparent affinity (EC50: 30 nM) for presynaptic delta-opioid receptors, mediating inhibition of striatal [14C]acetylcholine release, than for presynaptic mu receptors. However, whereas Leu-enkephalin had a similar apparent affinity for presynaptic and adenylate cyclase-coupled delta receptors, Met-enkephalin displayed a 30-fold selectivity toward the latter receptors. Studying the inhibitory effect of Met-enkephalin on striatal adenylate cyclase stimulated by endogenously released (amphetamine-induced) DA, its very high affinity appeared to be inversely related to the activation of inhibitory DA D-2 receptors. These data reveal a unique agonist affinity profile of interacting adenylate cyclase-coupled mu and delta receptors, mediating postsynaptic inhibition of dopaminergic neurotransmission in rat striatum, with the naturally occurring opioid peptide Met-enkephalin as a highly selective agonist. The permissive role of DA D-2 receptors is discussed.

Original languageEnglish
Pages (from-to)205-210
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume267
Issue number1
Publication statusPublished - 1 Jan 1993

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