Effect of nucleoside transport blockade on the interstitial adenosine level characterized by a novel method in guinea pig atria.
Several accepted methods are available to estimate the adenosine (Ado) concentration of interstitial fluid ([Ado]ISF) in functioning heart, providing results spanning over nano- to micromolar concentrations. This extremely large range points to the necessity of novel approaches for estimating [Ado]ISF or at least the alteration from basal [Ado]ISF. In the present study, the change in [Ado]ISF was characterized following nucleoside transport (NT) blockade elicited by 10 micromol/L dipyridamole or 10 micromol/L nitrobenzylthioinosine in isolated guinea pig atria, by means of our novel procedure referred to as receptorial responsiveness method (RRM). The RRM provided an index of the change in [Ado]ISF under NT blockade, namely the concentration of N-cyclopentyladenosine (CPA; a relatively stable A1 Ado receptor agonist), which is equieffective with the change in [Ado]ISF regarding the contractility. Our results show that dipyridamole or nitrobenzylthioinosine produced an elevation in [Ado]ISF at the cardiomyocyte A1 Ado receptors equivalent to about 16 or 20 nmol/l CPA, respectively. In addition, nitrobenzylthioinosine was found more appropriate for selective NT blockade than dipyridamole.
Karsai
Dénes
D
Department of Pharmacology, University of Debrecen, Debrecen, Hungary.
Zsuga
Judit
J
Juhász
Béla
B
Dér
Péter
P
Szentmiklósi
András József
AJ
Tósaki
Arpád
A
Gesztelyi
Rudolf
R
D000241:Adenosine / Q000031:analogs & derivatives / Q000032:analysis* / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004176:Dipyridamole / Q000494:pharmacology*; D045604:Extracellular Fluid / Q000737:chemistry*; D006168:Guinea Pigs; D006325:Heart Atria / Q000737:chemistry*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009705:Nucleosides / Q000378:metabolism*; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D009705:Nucleosides; C048599:N(6)-cyclopentyladenosine; D013868:Thioinosine; D004176:Dipyridamole; C001789:4-nitrobenzylthioinosine; D000241:Adenosine