| Popis: |
Binding of two phenothiazine neurolepties, chlorpromazine (CPZ) and thioproperazine (TPZ) was studied with rat liver and human leukocytes as sources of tissue and mitochondria. After 10 min of incubation at 24° in 15 or 30μg CPZ/ml Hank's solution, rat liver bound 66–88 per cent, whereas human leukocytes bound 27–29 per cent of the drug. Eight sequential centrifugal washings of the rat liver tissue released 30 per cent of the CPZ, but under the same conditions human leukocytes released 84–100 per cent of the bound drug. In contrast, we observed no difference in mitochondrial binding due to difference between tissues. Liver and leukoeyte mitochondria were centrifuged at 8° through linear sucrose density gradients that contained a constant concentration of 15 or 30μg phenothiazine/ml. After 5 min of centrifugation through a sucrose gradient containing 15 μg ifCPZ/ml, 3.7 μg ifCPZ/ml was ifbound/mg mitochondrial protein; after 15 min, 5.3 μg drug/ml was bound/mg protein. With 30 μg CPZ/ml in the gradient, 2.2 and 9.9 μg of drug/ml were bound/mg protein after 5 and 15 min, respectively. If TPZ, at either 15 or 30 μg/ml, was present in the gradient, 3.0 and 4.4μg of drug/ml were bound/mg protein after 5 and 15 min. Cooperative effects on binding by the mitochondria and the drugs were observed as a function of duration of exposure at 8°. Significant quantities of each drug, measured spectrophotofluorimetrically, were removed from solution by the mitochondrial suspensions. |
