Blockade of D-2 dopamine receptors strongly enhances the potency of enkephalins to inhibit dopamine-sensitive adenylate cyclase in rat neostriatum: involvement of delta- and mu-opioid receptors

• Published in: The Journal of neuroscience Vol. 6; no. 8; pp. 2235 - 2239
• Main Authors: Schoffelmeer, AN, Hansen, HA, Stoof, JC, Mulder, AH
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 01-08-1986; Society for Neuroscience
• Subjects: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Adenylyl Cyclase Inhibitors; Animals; Benzazepines - pharmacology; Corpus Striatum - drug effects; Corpus Striatum - enzymology; Cyclic AMP - metabolism; Dopamine - pharmacology; Enkephalin, D-Penicillamine (2,5); Enkephalin, Leucine - analogs & derivatives; Enkephalin, Leucine - pharmacology; Enkephalin, Leucine-2-Alanine; Enkephalins - pharmacology; Ergolines - pharmacology; Male; Morphine - pharmacology; Naloxone - pharmacology; Quinpirole; Rats; Rats, Inbred Strains; Receptors, Dopamine - drug effects; Receptors, Opioid - metabolism; Receptors, Opioid, delta; Receptors, Opioid, mu
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.06-08-02235.1986

The interactions between dopamine receptors and opioid receptors coupled to adenylate cyclase in rat neostriatum were investigated. cAMP efflux from neostriatal slices induced by simultaneous activation of (stimulatory) D-1 and (inhibitory) D-2 dopamine receptors with 30 microM dopamine was inhibited by the preferential delta-opioid receptor agonist [D-Ala2-D-Leu5] enkephalin (DADLE) and the mu-opioid receptor agonist morphine with an EC50 of 100 and 800 nM, respectively. On selective D-1 receptor activation (i.e., with D-2 receptors blocked by 10 microM (-)sulpiride), the EC50 of DADLE was strongly reduced to 3 nM, whereas that of morphine was unaffected. When D-1 and D-2 receptors were activated simultaneously, the inhibitory effects of DADLE (0.3 microM) and morphine (3 microM) on cAMP efflux were antagonized equally well by naloxone, a mu-opioid receptor antagonist. In contrast, on selective D-1 receptor activation, naloxone was about 20 times more potent in antagonizing the inhibitory effect of morphine than DADLE. Moreover, the delta-opioid receptor antagonist ICI 174864 (0.75 microM) did not affect the inhibitory effect of morphine but antagonized that of DADLE, provided that D-2 receptors were blocked. The highly selective delta-opioid receptor agonist [D-Pen2-D-Pen5] enkephalin (DPDPE) inhibited dopamine-stimulated cAMP efflux only when D-2 receptors were blocked. Similar results were obtained when the agonists SKF 38393 and LY 141865 were used to activate D-1 and D-2 receptors, respectively. These data indicate that blockade of D-2 receptors in the neostriatum elicits the coupling of delta-opioid receptors to dopamine-sensitive adenylate cyclase, thereby making it considerably more sensitive to inhibition by the enkephalins.