Transient Ischemia in the Presence of an Adenosine Deaminase Plus a Nucleoside Transport Inhibitor Confers Protection Against Contractile Depression Produced by Hydrogen Peroxide. Possible Role of Glycogen

1996 ◽  
Vol 28 (5) ◽  
pp. 1165-1176 ◽  
Author(s):  
X Gan
Keyword(s):  
Hydrogen Peroxide ◽  
Adenosine Deaminase ◽  
Nucleoside Transport ◽  
Transient Ischemia ◽  
Transport Inhibitor ◽  
Nucleoside Transport Inhibitor

Nitrobenzylthioinosine: an in vivo inhibitor of pig erythrocyte energy metabolism

1986 ◽  
Vol 251 (1) ◽  
pp. C90-C94 ◽  
Author(s):  
J. D. Young ◽  
S. M. Jarvis ◽  
A. S. Clanachan ◽  
J. F. Henderson ◽  
A. R. Paterson
Keyword(s):  
Potential Role ◽  
Metabolic Energy ◽  
Nucleoside Transport ◽  
Transport Activity ◽  
Dramatic Decrease ◽  
Transport Inhibitor ◽  
Nucleoside Transport Inhibitor ◽  
Plasma Adenosine

The potential role of plasma nucleosides as metabolic energy substrates for pig erythrocytes, which are impermeable to glucose, was investigated in vivo by infusion of anesthetized pigs with nitrobenzylthioinosine phosphate (NBMPR-P), a soluble prodrug form of the specific nucleoside transport inhibitor, nitrobenzylthioinosine. NBMPR-P administration (1 or 10 mg X kg-1 X h-1) led to complete in vivo blockade of erythrocyte nucleoside transport activity and was associated with a dramatic decrease in the erythrocyte [ATP]-to-[ADP] ratio from 11.4 at time 0 to 2.9 after 4 h (mean results from 3 animals). Plasma inosine concentrations increased progressively from 2-4 microM at time 0 to 20-70 microM after 4 h of drug administration. In contrast, plasma adenosine concentrations remained less than 0.4 microM in all samples. These data suggest that pig erythrocytes utilize plasma inosine as their physiological energy substrate.

Prevention of Catecholamine-Induced Cardiac Damage and Death with a Nucleoside Transport Inhibitor

1992 ◽  
Vol 20 (2) ◽  
pp. 173-178 ◽  
Author(s):  
Herman Van Belle ◽  
Willy Verheyen ◽  
Kris Ver Donck ◽  
Paul A. J. Janssen ◽  
J. Ian S. Robertson
Keyword(s):  
Nucleoside Transport ◽  
Cardiac Damage ◽  
Transport Inhibitor ◽  
Nucleoside Transport Inhibitor

scholarly journals The 2-chlorodeoxyadenosine-induced cell death signalling pathway in human thymocytes is different from that induced by 2-chloroadenosine

1995 ◽  
Vol 311 (2) ◽  
pp. 585-588 ◽  
Author(s):  
Z Szondy
Keyword(s):  
Cell Death ◽  
Nucleoside Transport ◽  
Signalling Pathways ◽  
Deoxycytidine Kinase ◽  
Induce Cell Death ◽  
Kinase C ◽  
Transport Inhibitor ◽  
Dependent Cell ◽  
Nucleoside Transport Inhibitor ◽  
Induced Apoptosis

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.

Activation of neuronal adenosine A1 receptors suppresses secretory reflexes in the guinea pig colon

1999 ◽  
Vol 276 (2) ◽  
pp. G451-G462 ◽  
Author(s):  
Helen J. Cooke ◽  
Y.-Z. Wang ◽  
C. Y. Liu ◽  
H. Zhang ◽  
F. L. Christofi
Keyword(s):  
Guinea Pig ◽  
Adenosine Deaminase ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Chloride Secretion ◽  
Nucleoside Transport ◽  
Muscularis Mucosa ◽  
Protein Gene Product ◽  
S 100 ◽  
Nucleoside Transport Inhibitor

The role of adenosine A1 receptors (A1R) in reflex-evoked short-circuit current ( I sc) indicative of chloride secretion was studied in the guinea pig colon. The A1R antagonist 8-cyclopentyltheophylline (CPT) enhanced reflex-evoked I sc. Adenosine deaminase and the nucleoside transport inhibitor S-(4-nitrobenzyl)-6-thioinosine enhanced and reduced reflex-induced I sc, respectively. The A1R agonist 2-chloro- N 6-cyclopentyladenosine (CCPA) inhibited reflex-evoked I sc at nanomolar concentrations, and its action was antagonized by CPT. In the presence of either N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide to block the 5-hydroxytryptamine (5-HT)-mediated pathway or piroxicam to block the prostaglandin-mediated pathway, CCPA reduced the residual reflex-evoked I sc. CCPA reduced the response to a 5-HT pulse without affecting the tetrodotoxin-insensitive I sc responses to carbachol or forskolin. Immunoreactivity for A1R was detected in the membrane (10% of neurons) and cytoplasm (90% of neurons) of neural protein gene product 9.5-immunoreactive (or S-100-negative) submucosal neurons, in glia, and in the muscularis mucosa. A1R immunoreactivity in a majority of neurons remained elevated in the cytoplasm despite preincubation with adenosine deaminase or CPT. A1R immunoreactivity colocalized in synaptophysin-immunoreactive presynaptic varicose nerve terminals. The results indicate that endogenous adenosine binding to high-affinity A1R on submucosal neurons acts as a physiological brake to suppress reflex-evoked I scindicative of chloride secretion.

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

1973 ◽  
Vol 51 (5) ◽  
pp. 666-672 ◽  
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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