Kappa receptor regulation of dopamine release from striatum and cortex of rats and guinea pigs

Document Type

Journal Article

Publication Date

1-1-1988

Journal

Journal of Pharmacology and Experimental Therapeutics

Volume

246

Issue

1

Abstract

The effects of opioid agonists with selectively for kappa, mu and delta types of opioid receptors on the K+-stimulated release of [3H]dopamine (DA) from striatum and cortex of rat and guinea pig loaded previously with the monoamine have been studied. The kappa agonist U50488H did not affect base-line release of [3H]DA measured in 5 mM K+, but produced a dose-dependent inhibition of the release of [3H]DA stimulated by 20 mM K+ from slices of striatum in rat and guinea pig, with an IC50 of about 0.5 nM in each case. In contrast, the mu-selective agonist, Tyr-D-Ala-Gly-(Me)Phe-Gly-ol, and the delta-selective agonist, [D-Pen2-D-Pen5]enkephalin, did not inhibit stimulated release from the slice preparations at concentrations up to 1 μM. The inhibitory effects of U50488H were antagonized by naloxone, and the potent and selective kappa antagonist, nor-binaltorphimine (nor-BNI). Similar results were obtained when release of [3H]DA from rat and guinea pig cortex slices was examined. In guinea pig cortex, the maximum inhibition of DA release induced by U50488H was 80% of control-stimulated fractional release. In rat cortex and in striatum of both species the maximum release was about 40% of control fractional release. Thus, in the guinea pig, the mesocortical dopaminergic pathway appears more sensitive to the inhibitory effects of U50488H than the nigrostriatal system. The effects of the opioids on the K+ (12.5 mM)-stimulated release of [3H]DA from guinea pig striatal synaptosomes also were determined. Again, U50488H was a potent inhibitor of stimulated release, suggesting that the inhibitory effect of U50488H was exerted directly on the terminals of the dopaminergic neurons. The effect of U50488H in the synaptosomal preparations was antagonized by naloxone, and Tyr-D-Ala-Gly-(Me)Phe-Gly-ol and [D-Pen3-D-Pen5]enkephalin were much less potent in inhibiting [3H]DA release. These results suggest that the terminal fields of both the nigrostriatal and mesocortical dopaminergic pathways in rat and guinea pig carry kappa-type opioid receptors which are capable of exerting an inhibitory regulation on stimulated DA release.

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