Presence of D4 dopamine receptors in human prefrontal cortex: a postmortem study.
OBJECTIVE
The aim of our study was to explore the presence and the distribution of D4 dopamine receptors in postmortem human prefrontal cortex, by means of the binding of [3H]YM-09151-2, an antagonist that has equal affinity for D2, D3 and D4 receptors. It was therefore necessary to devise a unique assay method in order to distinguish and detect the D4 component.


METHODS
Frontal cortex samples were harvested postmortem, during autopsy sessions, from 5 subjects. In the first assay, tissue homogenates were incubated with increasing concentrations of [3H]YM-09151-2, whereas L-745870, which has a high affinity for D4 and a low affinity for D2/D3 receptors, was used as the displacer. In the second assay, raclopride, which has a high affinity for D2/D3 receptors and a low affinity for D4 receptors, was used to block D2/D3. The L-745870 (500 nM) was added to both assays in order to determine the nonspecific binding.


RESULTS
Our experiments revealed the presence of specific and saturable binding of [3H]YM-09151-2. The blockade of D2 and D3 receptors with raclopride ensured that the D4 receptors were labeled. The mean maximum binding capacity was 88 +/- 25 fmol/mg protein, and the dissociation constant was 0.8 +/- 0.4 nM.


CONCLUSIONS
Our findings, although not conclusive, suggest that the density of D4 receptors is low in the human prefrontal cortex.
Marazziti
Donatella
D
Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, Pisa, Italy. dmarazzi@psico.med.unipi.it
Lucacchini
Antonio
A
Baroni
Stefano
S
Betti
Laura
L
Catena
Mario
M
Giannaccini
Gino
G
Dell'Osso
Bernardo
B
Masala
Irene
I
Mungai
Francesco
F
Dell'Osso
Liliana
L
D001549:Benzamides / Q000494:pharmacology*; D001923:Brain Chemistry; D002102:Cadaver; D018492:Dopamine Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000737:chemistry*; D050638:Receptors, Dopamine D4 / Q000032:analysis*
D001549:Benzamides; D018492:Dopamine Antagonists; D050638:Receptors, Dopamine D4; C030265:nemonapride