Substrates for cytochrome P450-2D1 exhibit a high affinity for σ binding sites suggesting that σ sites may be associated with the cytochrome P450-2D1 isozyme. In contrast to Sprague-Dawley, Dark Agouti rat liver does not express the P450-2D1 gene product. Therefore, if a subpopulation of σ sites is associated with the P450-2D1 enzyme, then the number (Bmax) of σ sites is predicted to be decreased in Dark Agouti brain and liver compared to Sprague-Dawley tissues. In the present study, binding of [3H](+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ([3H](+)3-PPP) in brain and liver from Dark Agouti, Sprague-Dawley, Long Evans and Wistar rat strains was examined. Results demonstrate marked variation in Bmax among the strains, with a consistently lower value for Dark Agouti tissues. However, the absolute difference in σ binding between brain and liver for each strain was not consistent with reported differences in the activity or levels of P450-2D1. Additionally, the percentage decrease in Bmax for Dark Agouti liver was found to be similar to that for Dark Agouti brain. Taken together these results suggest that P450-2D1 does not account for the strain-related difference in σ binding; but rather, other genetic factor(s) may be responsible for the decrease in the number of σ sites in the Dark Agouti strain compared to the other rat strains examined.
|Number of pages||6|
|Journal||European Journal of Pharmacology|
|State||Published - Oct 26 1993|
Bibliographical noteFunding Information:
The authors thank G. Dhillon and A.O. Hernandez for technical assistance and E.J. Pavlik for liberal use of the scintillation counter. Support for A.J. was provided by an American Foundation for Pharmaceutical Education Fellowship. This study was supported in part by a University of Kentucky Medical Center Small Research grant and U.S.P.H.S. grant DA 07219 awarded to L.D.
- (Dark Agouti rat)
- Cytochrome P450
- σ Binding
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