D-2 dopamine receptors and modulation of spontaneous acetylcholine (ACh) release from rat striatal synaptosomes

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 [H-3]-acetylcholine ([H-3]-ACh) release were investigated in rat striatal synaptosomes. 2 Quinpirole and 7-OH-DPAT inhibited in a concentration-dependent manner the basal efflux of [H-3]- 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 pEC(50) (-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 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 investigated in rat striatal synaptosomes. 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 [H-3]-YM-09151-2 to membranes of striatal synaptosomes and cells expressing D-2 and D-3 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 D-2 receptors (8.81+/-0.05), but the pK(i) value from cells expressing D-3 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 [H-3]-ACh efflux and this effect is competitively antagonized by haloperidol and probably mediated through dopamine D-2 receptors.