Mv. Clos et al., D-2 DOPAMINE-RECEPTORS AND MODULATION OF SPONTANEOUS ACETYLCHOLINE (ACH) RELEASE FROM RAT STRIATAL SYNAPTOSOMES, British Journal of Pharmacology, 122(2), 1997, pp. 286-290
1 The effect of two D-3/2 dopamine receptor agonists, LY-171555 (quinp
irole) and 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) on sp
ontaneous [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 sim
ilar 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-O
H-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 diff
erent from unity (0.85+/-0.05 and 1.17+/-0.11, respectively) and conse
quently 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 o
f 7-OH-DPAT). 5 Specific binding of [H-3]-YM-09151-2 to membranes of s
triatal synaptosomes and cells expressing D-2 and D-3 dopamine recepto
rs was inhibited by haloperidol. Analysis of competition curves reveal
ed the existence of a single population of receptors. There were no di
fferences between the estimated pK(i)(-log of molar concentration) val
ues 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 conclusio
n, the data obtained in the present study indicate that quinpirole and
7-OH-DPAT, two D-3/2 dopamine receptor agonists, inhibit the spontane
ous [H-3]-ACh efflux and this effect is competitively antagonized by h
aloperidol and probably mediated through dopamine D-2 receptors.