D<inf>2</inf> dopamine receptors and modulation of spontaneous acetylcholine (ACh) release from rat striatal synaptosomes

M. V. Clos, A. García-Sanz, N. M. Vivas, A. Badia

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)

Abstract

1. The effect of two D(3/2) dopamine receptor agonists, LY-171555 (quinpirole) and 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) on spontaneous [3H]-acetylcholine ([3H]-ACh) release were investigated in rat striatal synaptosomes. 2. Quinpirole and 7-OH-DPAT inhibited in a concentration-dependent manner the basal efflux of [3H]-ACh with similar E(max) (maximal inhibitory effect) values (29.95 ± 2.91% and 33.19 ± 1.21%, respectively). Significant differences were obtained between the pEC50 (-log of molar concentration) of quinpirole (7.87 ± 0.12) and 7-OH-DPAT (7.21 ± 0.17; P < 0.01). 3. Different concentrations (0.3-10 nM) of haloperidol (D(2/3) dopamine receptor antagonist) shifted to the right the concentration-response curves elicited by quinpirole and 7-OH-DPAT, without modifications in the E(max). 4. Slopes of a Schild plot obtained with haloperidol in the presence of quinpirole and 7-OH-DPAT were not significantly different from unity (0.85 ± 0.05 and 1.17 ± 0.11, respectively) and consequently haloperidol interacted with a homogeneous receptor population. The pK(B) values of haloperidol obtained from Schild regression were 9.96 ± 0.15 (in presence of quinpirole) and 9.90 ± 0.09 (in presence of 7-OH-DPAT). 5. Specific binding of [3H]-YM-09151-2 to membranes of striatal synaptosomes and cells expressing D2 and D3 dopamine receptors was inhibited by haloperidol. Analysis of competition curves revealed the existence of a single population of receptors. There were no differences between the estimated pK(i) (-log of molar concentration) values for synaptosomes (8.96 ± 0.02) and cells expressing D2 receptors (8.81 ± 0.05), but the pK(i), value from cells expressing D3 dopamine receptors differed significantly (8.48 ± 0.06; P < 0.01). 6. In conclusion, the data obtained in the present study indicate that quinpirole and 7-OH-DPAT, two D(3/2) dopamine receptor agonists, inhibit the spontaneous [3H]-ACh efflux and this effect is competitively antagonized by haloperidol and probably mediated through dopamine D2 receptors.
Original languageEnglish
Pages (from-to)286-290
JournalBritish Journal of Pharmacology
Volume122
DOIs
Publication statusPublished - 1 Oct 1997

Keywords

  • 7-OH-DPAT
  • D dopamine receptors 2
  • D dopamine receptors 3
  • Haloperidol
  • Presynaptic dopamine receptors
  • Quinpirole
  • Spontaneous ACh release
  • Synaptosomes

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