Presynaptic effect of 7-OH-DPAT on evoked [ 3H]-acetylcholine release in rat striatal synaptosomes

Abstract

The objective of the present experiments was to study the presynaptic effect of 7-hydroxy- N, N-di- n-propyl-2-aminotetraline (7-OH-DPAT, a D 2-like dopamine receptor agonist) on [ 3H]-acetylcholine ([ 3H]-ACh) release induced by potassium (15 mM, 25 mM and 60 mM), potassium channel-blockers (4-aminopyridine, 4-AP; tetraethylammonium, TEA and quinine) and veratridine to gain insight into the mechanisms involved in the activation of the D 2 dopamine-receptor subtype located at striatal cholinergic nerve terminals. 7-OH-DPAT (1 μM) inhibited the evoked [ 3H]-ACh release induced by K + 15 mM in a similar percentage than that obtained during basal conditions (30% and 27%, respectively). Nevertheless, in the presence of 25 mM and 60 mM of K + the inhibitory effect of 7-OH-DPAT was completely abolished. 4-AP (1–100 μM) and TEA (1 and 5 mM) significantly enhanced [ 3H]-ACh release, showing 69.32%±7.60% ( P<0.001) and 52.27%±5.64% ( P<0.001), respectively, at the highest concentrations tested. In these conditions, 7-OH-DPAT (1 μM) inhibited the release induced by potassium channel-blockers ∼25–27%. Quinine (0.1–1 μM) did not alter [ 3H]-ACh release either in the presence or absence of 7-OH-DPAT. Veratridine 10 μM evoked [ 3H]-ACh release in the presence of a low-calcium medium, but in such conditions 7-OH-DPAT (1 μM) did not modify the neurotransmitter release in the absence or presence of veratridine. Present data indicate that activation of the presynaptic D 2 dopamine receptor inhibits the [ 3H]-ACh release by increasing K + conductance, as high K + concentrations abolished the inhibitory control of 7-OH-DPAT on [ 3H]-ACh release. This effect could be mediated by potassium channels different from those sensitive to 4-AP, TEA and quinine. In addition, the presynaptic D 2 dopamine-receptor activation seems to not involve changes in intracellular Ca 2+.