The nucleoside-transport inhibitor soluflazine (R 64 719) increases the effects of adenosine in the guinea-pig hippocampal slice and is antagonized by adenosine deaminase

1987 ◽  
Vol 142 (3) ◽  
pp. 403-408 ◽  
Author(s):  
David Ashton ◽  
Roland Willems ◽  
Eric De Prins ◽  
Herman Van Belle ◽  
Albert Wauquier
Keyword(s):  
Guinea Pig ◽  
Adenosine Deaminase ◽  
Hippocampal Slice ◽  
Nucleoside Transport ◽  
Transport Inhibitor ◽  
Nucleoside Transport Inhibitor

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.

scholarly journals An Advanced in Silico Modelling of the Interaction between FSCPX, an Irreversible A1 Adenosine Receptor Antagonist, and NBTI, a Nucleoside Transport Inhibitor, in the Guinea Pig Atrium

Molecules ◽  
2019 ◽  
Vol 24 (12) ◽  
pp. 2207 ◽  
Author(s):  
Adrienn Monika Szabo ◽  
Tamas Erdei ◽  
Gabor Viczjan ◽  
Rita Kiss ◽  
Judit Zsuga ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Adenosine Receptor ◽  
In Silico ◽  
Ex Vivo ◽  
Nucleoside Transport ◽  
A1 Adenosine Receptor ◽  
Adenosine Receptor Antagonist ◽  
Transport Inhibitor ◽  
Guinea Pig Atrium ◽  
Nucleoside Transport Inhibitor

In earlier studies, we generated concentration-response (E/c) curves with CPA (N6-cyclopentyladenosine; a selective A1 adenosine receptor agonist) or adenosine, in the presence or absence of S-(2-hydroxy-5-nitrobenzyl)-6-thioinosine (NBTI, a selective nucleoside transport inhibitor), and with or without a pretreatment with 8-cyclopentyl-N3-[3-(4-(fluorosulfonyl)-benzoyloxy)propyl]-N1-propylxanthine (FSCPX, a chemical known as a selective, irreversible A1 adenosine receptor antagonist), in isolated, paced guinea pig left atria. Meanwhile, we observed a paradoxical phenomenon, i.e., the co-treatment with FSCPX and NBTI appeared to enhance the direct negative inotropic response to adenosine. In the present in silico study, we aimed to reproduce eight of these E/c curves. Four models (and two additional variants of the last model) were constructed, each one representing a set of assumptions, in order to find the model exhibiting the best fit to the ex vivo data, and to gain insight into the paradoxical phenomenon in question. We have obtained in silico evidence for an interference between effects of FSCPX and NBTI upon our ex vivo experimental setting. Regarding the mechanism of this interference, in silico evidence has been gained for the assumption that FSCPX inhibits the effect of NBTI on the level of endogenous (but not exogenous) adenosine. As an explanation, it may be hypothesized that FSCPX inhibits an enzyme participating in the interstitial adenosine formation. In addition, our results suggest that NBTI does not stop the inward adenosine flux in the guinea pig atrium completely.

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.

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