Stereoselective high-affinity binding of 3H-alaproclate to membranes from rat cerebral cortex.
The binding of 3H-alaproclate, a selective 5-hydroxytryptamine uptake inhibitor, to membranes prepared from the rat cerebral cortex was investigated by a filtration technique. It was found that 3H-alaproclate bound with high affinity to three or four different sites and to one low affinity site. The binding to two of these sites was displaceable by 1 microM proadifen (SKF 525A), an inhibitor of drug metabolism. From iterative nonlinear regression analysis the KD-values of these sites were calculated to about 1 and 28 nM and the Bmax values 1.5 and 19 pmol/g wet tissue, respectively. The high affinity binding that was not displaceable by proadifen but by 10 microM alaproclate had KD-values of 1 nM and 6 nM and Bmax-values of 0.4 and 2 pmol/g wet tissue. The low affinity binding that was not displaceable by proadifen had a KD-value of about 200 nM and a Bmax-value of about 90 pmol/g tissue. The possible relationship between the proadifen sensitive high affinity binding of 3H-alaproclate and the brain cytochrome P-450 is discussed.
Research and Development Laboratories, Astra Alab AB, Södertälje, Sweden.
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Ross
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Gawell
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D000409:Alanine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000378:metabolism*; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
D000928:Antidepressive Agents; D011335:Proadifen; C025293:alaproclate; D000409:Alanine; D007099:Imipramine