Opioid receptor-mediated inhibition of 3H-dopamine and 14C-acetylcholine release from rat nucleus accumbens slices
The release of 14C-ACh from rat nucleus accumbens slices, induced by 15 mM [K+], was inhibited by the µ- and δ-opioid agonists DAMGO and DPDPE, respectively, whereas only the κ agonist U50,488 reduced the release of 3H-DA.
The opioid receptors involved appear to be localized on nerve terminals, since blockade of action potential propagation by 1 μM TTX did not diminish the inhibitory effects of DAMGO, DPDPE or U50,488.
Enhancement of the potassium concentration in the superfusion medium to 56 mM with simultaneous reduction of the Ca2+ concentration from 1.2 mM to 0.12 mM induced a release similar to that caused by 15 mM K+ and 1.2 mM Ca+. Under this conditions, the inhibitory effects of both DAMGO and DPDPE on stimulated 14C-ACh release were reduced, whereas the inhibition of evoked 3H-DA release caused by U50,488 was not affected. Activation of µ- as well as δ-opioid receptors by DAMGO and DPDPE, respectively, inhibited forskolin-stimulated adenylate cyclase activity. However, increasing the intracellular cAMP levels with 0.3 mM 8-bromo-CAMP affected neither the depolarization-induced release of 14C-ACh or 3H-DA from accumbens slices nor the inhibitory effects of opioid receptor activation thereon.
The results indicate that the mechanism by which functional µ- and δ receptors presynaptically inhibit the depolarization-induced 14C-ACh release from nucleus accumbens slices is likely to involve an increase of potassium channel conductance. In contrast, activation of κ-opioid receptors, which inhibits depolarization-evoked 3H-DA release, apparently does not result in a hyperpolarization of (dopaminergic) nerve terminals. In none of these inhibitory effects presynaptic adenylate cyclase appears to be involved.
Key wordsOpioid receptor types Dopamine release Acetylcholine release Potassium channels Adenylate cyclase
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