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

A. Garcia Sanz, S. Hospital, A. Badia, M. Y. Clos

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13 Citations (Scopus)

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 D2-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 D2 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 D2 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 D2 dopamine-receptor activation seems to not involve changes in intracellular Ca2+. (C) 2000 Elsevier Science B.V.
Original languageEnglish
Pages (from-to)116-122
JournalBrain Research
Volume874
DOIs
Publication statusPublished - 25 Aug 2000

Keywords

  • 4- AP
  • 7-OH-DPAT
  • Evoked-[ H]-ACh release 3
  • Potassium channel-blocker
  • Presynaptic D dopamine receptor 2
  • Quinine
  • TEA

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