[(3)H]-YM-09151-2 binding sites in human brain postmortem.
The controversial and limited data on the distribution of dopamine (DA) receptors of type 4 (D(4)) in the human brain prompted us to explore their density and pharmacological characteristics in the prefrontal cortex, striatum and hippocampus, through a series of binding assays. Brain samples were taken during autopsy from seven subjects. Tissue homogenates were incubated with increasing concentration of [(3)H]-YM-09151-2, a D(2)-like receptor antagonist, and L-745,870 and/or sulpiride to define the non-specific binding, while PPAP was used to block sigma receptors. The results showed a low density of D(4) receptors in the hippocampus only, with a preponderance of D(2)/D(3) and sigma receptors in the prefrontal cortex and striatum. In conclusion, these findings underline that it is possible to label D(4) receptors by means of [(3)H]-YM-09151-2, provided that D(2), D(3) and sigma receptors are blocked.
Marazziti
Donatella
D
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, University of Pisa, Italy. dmarazzi@psico.med.unipi.it
Baroni
Stefano
S
Masala
Irene
I
Giannaccini
Gino
G
Betti
Laura
L
Palego
Lionella
L
Catena Dell'Osso
Mario
M
Consoli
Giorgio
G
Castagna
Maura
M
Lucacchini
Antonio
A
D000368:Aged; D001549:Benzamides / Q000493:pharmacokinetics / Q000494:pharmacology*; D001665:Binding Sites; D001923:Brain Chemistry / Q000502:physiology*; D003627:Data Interpretation, Statistical; D018492:Dopamine Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D011180:Postmortem Changes; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011437:Propylamines / Q000494:pharmacology; D020891:Raclopride / Q000493:pharmacokinetics; D050638:Receptors, Dopamine D4 / Q000187:drug effects; D017480:Receptors, sigma / Q000187:drug effects; D013469:Sulpiride / Q000493:pharmacokinetics
D001549:Benzamides; D018492:Dopamine Antagonists; D011437:Propylamines; D017480:Receptors, sigma; C068473:N-(3-phenyl-n-propyl)-1-phenyl-2-aminopropane; D050638:Receptors, Dopamine D4; D020891:Raclopride; D013469:Sulpiride; C030265:nemonapride