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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 μmol/L dipyridamole or 10 μmol/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 N6-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.