Opioid receptor antagonists discriminate between presynaptic mu and delta receptors and the adenylate cyclase-coupled opioid receptor complex in the brain

A. N M Schoffelmeer, T. J. De Vries, F. Hogenboom, Victor J Hruby, P. S. Portoghese, A. H. Mulder

Research output: Contribution to journalArticle

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Abstract

The present study addressed the question as to whether or not interacting mu and delta opioid receptors, which may constitute an opioid receptor complex-inhibitory coupled to adenylate cyclase in rat neostriatum, display different antagonistic properties than the classical (noncomplexed) mu and delta receptors. In concentrations that antagonized the presynaptic inhibitory effect of [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAMGO) on [3H]norepinephrine release from rat neocortical slices, the cyclic somatostatin-related mu opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn- Thr-Pen-Thr-NH2 did not affect the inhibition of dopamine-sensitive adenylate cyclase caused by DAMGO in neostriatal slices. The delta opioid receptor antagonist naltrindole appeared to be about 200-fold more effective as an antagonist against inhibitory effect of [D-Ser2(O-tert- butyl),Leu5]enkephalyl-Thr6 on [14C]acetylcholine release from neostriatal slices than against the inhibitory effect of DAMGO on [3H]norepinephrine release from neocortical slices, in agreement with the involvement of presynaptic delta and mu receptors; respectively. However, regarding the inhibitory effect of DAMGO and [D-Ser2(O-tert- butyl),Leu5]enkephalyl-Thr6 on adenylate cyclase activity in neostriatal slices, naltrindole not only displayed a very low affinity but also only 10- fold delta-selectivity. In striking contrast to D-Phe-Cys-Tyr-D-TRP-ORN-THR- PEN-THR-NH2 and naltrindole, naloxone did not discriminate between the neurotransmitter release- and adenylate cyclase-inhibitory effects of DAMGO and [D-Ser2(O-tert-butyl),Leu5]enkephalyl-Thr6. These data strongly suggest that interacting mu and delta receptors in rat neostriatum display pharmacological characteristics that are clearly different from (presynaptic) mu, delta and kappa receptors in the brain, and indicate that the putative opioid receptor complex may represent a pharmacologically unique type of opioid receptor.

Original languageEnglish (US)
Pages (from-to)20-24
Number of pages5
JournalJournal of Pharmacology and Experimental Therapeutics
Volume263
Issue number1
StatePublished - 1992
Externally publishedYes

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Presynaptic Receptors
delta Opioid Receptor
naltrindole
Narcotic Antagonists
mu Opioid Receptor
Opioid Receptors
Adenylyl Cyclases
Enkephalins
Brain
Neostriatum
Norepinephrine
kappa Opioid Receptor
Naloxone
Somatostatin
Acetylcholine
Neurotransmitter Agents
Dopamine
Pharmacology

ASJC Scopus subject areas

  • Pharmacology

Cite this

Opioid receptor antagonists discriminate between presynaptic mu and delta receptors and the adenylate cyclase-coupled opioid receptor complex in the brain. / Schoffelmeer, A. N M; De Vries, T. J.; Hogenboom, F.; Hruby, Victor J; Portoghese, P. S.; Mulder, A. H.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 263, No. 1, 1992, p. 20-24.

Research output: Contribution to journalArticle

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AU - Schoffelmeer, A. N M

AU - De Vries, T. J.

AU - Hogenboom, F.

AU - Hruby, Victor J

AU - Portoghese, P. S.

AU - Mulder, A. H.

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