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[3H]GBR-12935 binding to cytochrome P450 in the human brain.
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
1994 (Engelska)Ingår i: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 62, nr 1, s. 342-8Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The presence of multiple [3H]GBR-12935 binding sites in the human brain has been revealed in several recent studies. One site represents the dopamine uptake site. In rat brain it was demonstrated that [3H]GBR-12935 also binds to nondopaminergic "piperazine acceptor sites." One of these sites has been identified as cytochrome P450IID1 in canine brain. [3H]GBR-12935 binding to the piperazine acceptor sites in the human brain was investigated in the present study. A pharmacological definition of the piperazine acceptor sites is presented: the [3H]GBR-12935 binding fraction that could be discriminated by 10 microM GBR-12909 in the presence of 0.3 microM mazindol. This binding fraction was saturable, with binding affinity in the range of 3-8 nM. It was also demonstrated that the piperazine acceptor or cytochrome P450-sensitive drugs cis-flupentixol and proadifen (SKF 525 A) compete for the same binding sites, suggesting the cytochrome P450 nature of the binding. The findings presented support the proposal that at least part of this fraction represents cytochrome P450IID6, the human form of P450IID1. The distribution of [3H]GBR-12935 binding to the suggested P450IID6-site in 12 brain regions was examined, without significant differences in binding densities between the regions. The significance of the present findings on the cytochrome P450 system in brain is discussed.

Ort, förlag, år, upplaga, sidor
1994. Vol. 62, nr 1, s. 342-8
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URN: urn:nbn:se:umu:diva-36534PubMedID: 8263534OAI: oai:DiVA.org:umu-36534DiVA, id: diva2:354620
Tillgänglig från: 2010-10-04 Skapad: 2010-10-04 Senast uppdaterad: 2018-06-08

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