Characteristics of [3H]GBR 12935 binding in the human and rat frontal cortex.
Binding characteristics of the selective dopamine uptake inhibitor [3H]GBR 12935 have been described for the striatum but not for the frontal cortex. We have developed assay conditions for quantifying [3H]GBR 12935 binding in the frontal cortex. In both the rat and human frontal cortex, the assay required four times more tissue (8 mg/ml) than in the striatum (2 mg/ml). [3H]GBR 12935 binding in the frontal is complex, as it involves multiple binding sites. The high-affinity binding site is sodium dependent and is inhibited by sodium. In human but not in rat frontal cortex, addition of K+ reversed the sodium inhibition. The pharmacological profile of the high-affinity [3H]GBR 12935 binding site is consistent with that of the dopamine transporter, because drugs with the most selective dopamine reuptake blocking activities are the most potent displacers of [3H]GBR 12935 binding. There is a positive correlation between the rat and human inhibitory constants, a finding indicating that there are similar pharmacological profiles across at least these two species. Rats with a 6-hydroxydopamine lesion had a 47% decrease in number of [3H]GBR 12935 binding sites, a result indicating that at least a portion of these sites had been on presynaptic dopamine terminals.
Hitri
A
A
Neuropsychiatry Branch, NIMH Neurosciences Center, Washington, DC.
Venable
D
D
Nguyen
H Q
HQ
Casanova
M F
MF
Kleinman
J E
JE
Wyatt
R J
RJ
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D018492:Dopamine Antagonists; D005625:Frontal Lobe / Q000378:metabolism*; D006801:Humans; D006892:Hydroxydopamines; D009994:Osmolar Concentration; D016627:Oxidopamine; D010879:Piperazines / Q000378:metabolism*; D051381:Rats / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology; D014316:Tritium
D018492:Dopamine Antagonists; D006892:Hydroxydopamines; D010879:Piperazines; D014316:Tritium; D016627:Oxidopamine; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine; D012964:Sodium