Further evidence for a role of delta-opiate receptors in the presynaptic regulation of newly synthesized dopamine release.

The effects of the specific delta-agonist of opiate receptors, DTLET (Tyr-D-Thr-Gly-Phe-Leu-Thr), the specific mu-agonist DAGO (Tyr-D-Ala-Gly-(Me)Phe-Gly-ol) and of kelatorphan (N-((2R)-3-(hydroxyaminocarbonyl-2-benzyl-1-oxopropyl)-L-alanine), a potent inhibitor of the enkephalin-degrading enzymes, on the spontaneous release of [3H]dopamine ([3H]DA) synthesized from [3H]tyrosine were examined in rat striatal slices. DTLET (10(-7) M, 10(-6) M) and kelatorphan (5 X 10(-6) M) enhanced markedly the release of newly synthesized [3H]DA, while DAGO (10(-6) M) was inactive. The stimulatory effects of DTLET (10(-7) M) and kelatorphan (5 X 10(-6) M) were prevented in the presence of naloxone (3 X 10(-6) M; 10(-4) M respectively) or ICI 154,129 (10(-5) M), a selective antagonist of delta-opiate receptors. While DTLET (10(-7) M) stimulated the 30 mM potassium-evoked release of newly synthesized [3H]DA, it did not affect the potassium-evoked release of [3H]DA previously synthesized in tissues. A higher concentration of DTLET (10(-6) M) was required in the latter case. In contrast to the release observed with striatal slices, DTLET (10(-7) M), 10(-6) M) or DAGO (10(-6) M) did not affect the spontaneous release of newly synthesized [3H]DA from nucleus accumbens slices. In addition, DTLET (10(-6) M) was without effect on the potassium-evoked release of newly synthesized [3H]DA in this structure. The present results confirmed that delta-opiate receptors are involved in the presynaptic regulation of [3H]DA release.(ABSTRACT TRUNCATED AT 250 WORDS)