TY - JOUR T1 - Mu- and delta-opioid receptor-mediated inhibition of adenylate cyclase activity stimulated by released endogenous dopamine in rat neostriatal slices; demonstration of potent delta-agonist activity of bremazocine. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 864 LP - 868 VL - 249 IS - 3 AU - M H Heijna AU - F Hogenboom AU - P S Portoghese AU - A H Mulder AU - A N Schoffelmeer Y1 - 1989/06/01 UR - http://jpet.aspetjournals.org/content/249/3/864.abstract N2 - Rat neostriatal slices were superfused with medium containing 0.1 to 30 microM of the dopamine (DA)-releasing agent D-(+)-am-phetamine (AMPH) and the D-2 DA receptor antagonist (-)-sulpiride (10 microM) in the absence or presence of mu-, delta-, and kappa-selective opioids. AMPH dose-dependently enhanced the cyclic AMP production, as measured by its efflux from striatal slices, whereas simultaneous blockade of D-2 DA receptors by (-)-sulpiride strongly potentiated this effect. Both the mu-opioid receptor selective agonist [D-Ala2,MePhe4,Gly-ol5]enkephalin (0.01-3 microM) and the delta-opioid receptor selective agonist [D-Phe2-D-Pen5]enkephalin (DPDPE, 0.01-3 microM) inhibited the cyclic AMP efflux, stimulated by 10 microM AMPH in the presence of (-)-sulpiride, by 70 to 80%. The highly selective kappa-opioid receptor agonist U 50,488 (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrol-idinyl)- cyclohexyl]benzeneacetamide methanesulfonate hydrate) (0.01-1 microM) had no effect. In contrast, the purported kappa-opioid receptor agonist bremazocine (3-300 nM) inhibited the stimulated adenylate cyclase activity to a similar extent as did [D-Ala2-MePhe4,Gly-ol5]enkephalin and DPDPE. Moreover, the selective irreversible delta-antagonist fentanyl isothiocyanate reversed both the inhibition caused by DPDPE and that caused by bremazocine, whereas the kappa-selective antagonist norbinaltorphimine showed no differences in its potency to antagonize the inhibitory effects of the different opioid agonists. The results indicate that opioids, by activating mu- or delta-, but not kappa-opioid receptors may cause a profound inhibition of adenylate cyclase activity stimulated by activation of (postsynaptic) D-1 DA receptors upon the (presynaptic) release of DA.(ABSTRACT TRUNCATED AT 250 WORDS) ER -