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 [ 3 H]‐acetylcholine ([ 3 H]‐ACh) release were investigated in rat striatal synaptosomes. 2 Quinpirole and 7‐OH‐DPAT inhibited in a concentration‐dependent manner the basal efflux of [ 3 H]‐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 n M ) 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 signficantly different from unity (0.85±0.05 and 1.17±0.11, respectively) and consequently haloperidol interacted with a homogeneous receptor population. The p K 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 [ 3 H]‐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 p K i (−log of molar concentration) values for synaptosomes (8.96±0.02) and cells expressing D 2 receptors (8.81±0.05), but the p K 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 [ 3 H]‐ACh efflux and this effect is competitively antagonized by haloperidol and probably mediated through dopamine D 2 receptors.British Journal of Pharmacology (1997) 122 , 286–290; doi: 10.1038/sj.bjp.0701327