IDENTIFICATION OF D-3 AND SIGMA-RECEPTORS IN THE RAT STRIATUM AND NUCLEUS-ACCUMBENS USING (+ -)-7-HYDROXY-N,N-DI-N-[H-3] PROPYL-2-AMINOTETRALIN AND CARBETAPENTANE/
Dr. Wallace et Rm. Booze, IDENTIFICATION OF D-3 AND SIGMA-RECEPTORS IN THE RAT STRIATUM AND NUCLEUS-ACCUMBENS USING (+ -)-7-HYDROXY-N,N-DI-N-[H-3] PROPYL-2-AMINOTETRALIN AND CARBETAPENTANE/, Journal of neurochemistry, 64(2), 1995, pp. 700-710
Cross-reactions between dopamine D-3 and sigma receptor ligands were i
nvestigated using (+/-)-7-hydroxy-N,N-di-n-[H-3] propyl-2-aminotetrali
n [(+/-)-7-OH-[3H]-DPAT], a putative D-3-selective radioligand, in con
junction with the unlabeled sigma ligands 1,3-di(2-tolyl)guanidine (DT
G), carbetapentane, and R(-)-N-(3-phenyl-1-propyl)-1-phenyl-2-aminopro
pane [R(-)-PPAP]. In transfected CCL1.3 mouse fibroblasts expressing t
he human D-3 receptor, neither DTG nor carbetapentane (0.1 mu M) displ
aced (+/-)-7-OH-[H-3]DPAT binding. R(-)-PPAP (0.1 mu M) displaced 39.6
+/- 1.0% of total (+/-)-7-OH-[H-3]DPAT binding. In striatal and nucle
us accumbens homogenates, (+/-)-7-OH-[H-3]DPAT labeled a single site (
15-20 fmol/mg of protein) with high (1 nM) affinity. Competition analy
sis with carbetapentane defined both high- and low-affinity sites in s
triatal (35 and 65%, respectively) and nucleus accumbens (59 and 41%,
respectively) tissue, yet R(-)-PPAP identified two sites in equal prop
ortion. Carbetapentane and R(-)-PPAP (0.1 mu M) displaced similar to 2
0-50% of total (+/-)-7-OH-[H-3]DPAT binding in striatum, nucleus accum
bens, and olfactory tubercle in autoradiographic studies, with the nuc
leus accumbens shell subregion exhibiting the greatest displacement. T
o determine directly (+)-7-OH-[H-3]DPAT binding to sigma receptors, sa
turation analysis was performed in the cerebellum while masking D-3 re
ceptors with 1 mu M dopamine. Under these conditions (+)-7-OH-[3H]DPAT
labeled sigma receptors with an affinity of 24 nM. These results sugg
est that (a) (+/-)7-OH-[H-3]DPAT binds D-3 receptors with high affinit
y in rat brain and (b) a significant proportion of (+/-)-7-OH-[H-3]DPA
T binding consists of sigma(1) sites and the percentages of these site
s differ among the subregions of the striatum and nucleus accumbens.