title: 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.
abstract: The apparent affinities of endogenous opioid peptides for noncompetitively 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 microM DA in the presence of 10 microM 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. beta-Endorphin 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 microM) 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.(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: A H
authors.initials: AH
authors.lastname: Mulder
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D004723:Endorphins / Q000502:physiology*; D004745:Enkephalins / Q000494:pharmacology; D005283:Fentanyl / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D017879:Isothiocyanates / Q000494:pharmacology; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017465:Receptors, Opioid, delta / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000502:physiology*; D013469:Sulpiride / Q000494:pharmacology
chemical_list: D004723:Endorphins; D004745:Enkephalins; D017879:Isothiocyanates; D011480:Protease Inhibitors; D017447:Receptors, Dopamine D1; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D017661:Receptors, Presynaptic; D009270:Naloxone; D013469:Sulpiride; C037091:fentanyl isothiocyanate; D000262:Adenylyl Cyclases; D000109:Acetylcholine; D005283:Fentanyl; D004298:Dopamine; D009638:Norepinephrine