title: Effect of nucleoside transport blockade on the interstitial adenosine level characterized by a novel method in guinea pig atria.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Debrecen, Debrecen, Hungary.
authors.forename: Dénes
authors.initials: D
authors.lastname: Karsai
authors.forename: Judit
authors.initials: J
authors.lastname: Zsuga
authors.forename: Béla
authors.initials: B
authors.lastname: Juhász
authors.forename: Péter
authors.initials: P
authors.lastname: Dér
authors.forename: András József
authors.initials: AJ
authors.lastname: Szentmiklósi
authors.forename: Arpád
authors.initials: A
authors.lastname: Tósaki
authors.forename: Rudolf
authors.initials: R
authors.lastname: Gesztelyi
mesh_terms: 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
chemical_list: D009705:Nucleosides; C048599:N(6)-cyclopentyladenosine; D013868:Thioinosine; D004176:Dipyridamole; C001789:4-nitrobenzylthioinosine; D000241:Adenosine