title: Opioid receptor antagonists discriminate between presynaptic mu and delta receptors and the adenylate cyclase-coupled opioid receptor complex in the brain.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, Free University, Medical Faculty, Amsterdam, The Netherlands.
authors.forename: A N
authors.initials: AN
authors.lastname: Schoffelmeer
authors.forename: T J
authors.initials: TJ
authors.lastname: De Vries
authors.forename: F
authors.initials: F
authors.lastname: Hogenboom
authors.forename: V J
authors.initials: VJ
authors.lastname: Hruby
authors.forename: P S
authors.initials: PS
authors.lastname: Portoghese
authors.forename: A H
authors.initials: AH
authors.lastname: Mulder
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009019:Morphinans / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000187:drug effects*
chemical_list: D004745:Enkephalins; D007211:Indoles; D009019:Morphinans; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009271:Naltrexone; D000262:Adenylyl Cyclases; C055382:naltrindole; D000109:Acetylcholine; D009638:Norepinephrine