Sleep improvement in dogs after oral administration of mioflazine, a nucleoside transport inhibitor

2-chloroadenosine induced DNA fragmentation and cell death in human thymocytes primarily by Ca(2+)-dependent mechanisms. Incubation of human thymocytes with 2-chlorodeoxyadenosine (5-1000 nM) also induced cell death (apoptosis) which was dependent on macromolecule synthesis and involved activation of an endonuclease which was inhibited by Zn2+. The effect of 2-chlorodeoxyadenosine was prevented by addition of dipyridamole, a strong nucleoside transport inhibitor, or of deoxycytidine, previously shown to compete for uptake by deoxycytidine kinase. 2-Chlorodeoxyadenosine-induced apoptosis did not involve increases in the cytosolic Ca2+ concentration, but required the presence of intracellular Ca2+. It was not inhibited by activators of protein kinase C previously shown to inhibit Ca(2+)-dependent cell death. Addition of 2-chlorodeoxyadenosine induced an increase in the amount of p53 in human thymocytes, while 2-chloroadenosine had no effect. These data suggest that 2-chloroadenosine and 2-chlorodeoxyadenosine induce cell death in human thymocytes via different signalling pathways.

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Antibiotic C3368-A, a fungus-derived nucleoside transport inhibitor, potentiates the activity of antitumor drugs

Cancer Chemotherapy and Pharmacology ◽

10.1007/s002800050300 ◽

1995 ◽

Vol 36 (2) ◽

pp. 149-154

Author(s):

Jian Su ◽

Y.-S. Zhen ◽

Chang-qing Qi ◽

Ji-lan Hu

Keyword(s):

Nucleoside Transport ◽

Antitumor Drugs ◽

Transport Inhibitor ◽

Nucleoside Transport Inhibitor

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Binding of the Nucleoside Transport Inhibitor 4-Nitrobenzylthioinosine to Erythrocyte Membranes

Canadian Journal of Biochemistry ◽

10.1139/o73-083 ◽

1973 ◽

Vol 51 (5) ◽

pp. 666-672 ◽

Cited By ~ 41

Author(s):

M. A. Pickard ◽

R. R. Brown ◽

B. Paul ◽

A. R. P. Paterson

Keyword(s):

Binding Sites ◽

Nucleoside Transport ◽

Erythrocyte Membranes ◽

Affinity Binding ◽

Inhibitor Molecule ◽

High Affinity Binding ◽

High Affinity ◽

Transport Inhibitor ◽

Binding Data ◽

Nucleoside Transport Inhibitor

4-Nitrobenzylthioinosine (NBMPR), a potent nucleoside transport inhibitor, was prepared in two radioactive forms and the binding of these to erythrocyte ghosts was studied. Similar binding data were obtained with inhibitor containing 14C in the purine 8-position or in the benzyl 7-position, suggesting that the entire inhibitor molecule was bound. A saturable high-affinity mode of NBMPR binding was apparent; NBMPR bound in this way was not removed by washing, but was displaced by a related inhibitor of nucleoside transport, 2-hydroxy-5-nitrobenzylthioguanosine (HNBTGR). It is postulated that the high-affinity binding sites are the nucleoside transport elements of the erythrocyte membrane. From ghosts treated with 14C-NBMPR under conditions which assured binding of the high affinity type, 14C was recovered by extractions in the form of NBMPR. Thus, this mode of NBMPR binding is reversible and covalent linkages do not appear to be involved. A low affinity mode of NBMPR binding was also demonstrated; this appeared to be a partition of NBMPR between the medium and the membrane substance. This component of bound NBMPR was not displaced by HNBTGR and was removed by washing.

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