D2 dopamine receptors and modulation of spontaneous acetylcholine (ACh) release from rat striatal synaptosomes.

1. The effect of two D3/2 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 Emax (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 (D2/3 dopamine receptor antagonist) shifted to the right the concentration-response curves elicited by quinpirole and 7-OH-DPAT, without modifications in the Emax. 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 pKB 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 pKi (-log of molar concentration) values for synaptosomes (8.96 +/- 0.02) and cells expressing D2 receptors (8.81 +/- 0.05), but the pKi 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 D3/2 dopamine receptor agonists, inhibit the spontaneous [3H]-ACh efflux and this effect is competitively antagonized by haloperidol and probably mediated through dopamine D2 receptors.