title: Presence of D4 dopamine receptors in human prefrontal cortex: a postmortem study.
abstract: 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.
authors.affiliation: Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, Pisa, Italy. dmarazzi@psico.med.unipi.it
authors.forename: Donatella
authors.initials: D
authors.lastname: Marazziti
authors.forename: Antonio
authors.initials: A
authors.lastname: Lucacchini
authors.forename: Stefano
authors.initials: S
authors.lastname: Baroni
authors.forename: Laura
authors.initials: L
authors.lastname: Betti
authors.forename: Mario
authors.initials: M
authors.lastname: Catena
authors.forename: Gino
authors.initials: G
authors.lastname: Giannaccini
authors.forename: Bernardo
authors.initials: B
authors.lastname: Dell'Osso
authors.forename: Irene
authors.initials: I
authors.lastname: Masala
authors.forename: Francesco
authors.initials: F
authors.lastname: Mungai
authors.forename: Liliana
authors.initials: L
authors.lastname: Dell'Osso
mesh_terms: 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*
chemical_list: D001549:Benzamides; D018492:Dopamine Antagonists; D050638:Receptors, Dopamine D4; C030265:nemonapride