Binding of [G-3H]6-(4-nitrobenzylmercapto)purine ribonucleoside to isolated membranes. Inhibitory effect of mioflazine and its derivatives.
The binding of [G-3H]-6-(4-nitrobenzylmercapto)purine ribonucleoside [( G-3H]NBMPR) was investigated using a centrifugation assay with membrane preparations from hamster tissues including liver, lung, kidney and heart. Only liver and lung membranes showed high specific binding, with dissociation constants (Kd) values of 2.4 +/- 0.4 and 0.44 +/- 0.05 nM, and maximal binding (Bmax) of 3.7 +/- 0.4 and 1.04 +/- 0.01 pmol/mg, respectively. The binding of [G-3H]NBMPR was inhibited in a concentration dependent manner by unlabelled NBMPR, dilazep and a new group of chemically related nucleoside transport inhibitors, mioflazine, soluflazine and R57974, the latter being the most potent derivative. R57974 displaced bound [G-3H]NBMPR as effectively as unlabelled NBMPR suggesting a common binding site. The assay procedure used appears useful for the rapid screening of the effectiveness of nucleoside transport inhibitors which will be of value for the selection of inhibitors suitable for combination with cytotoxic nucleosides in the treatment of selected cancers or parasitic diseases.
Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
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Ogbunude
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Baer
D000818:Animals; D001665:Binding Sites; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism*; D006224:Cricetinae; D004109:Dilazep / Q000494:pharmacology; D066298:In Vitro Techniques; D007288:Inosine / Q000031:analogs & derivatives*; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D010879:Piperazines / Q000494:pharmacology*; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000378:metabolism
D002317:Cardiovascular Agents; D010879:Piperazines; D013868:Thioinosine; D007288:Inosine; C041518:mioflazine; D004109:Dilazep; C001789:4-nitrobenzylthioinosine