Hypoxanthine-tricyclano is a synthetic adenosine analogue, in which adenine and ribose have been replaced by hypoxanthine and a morpholino-derived tricyclic moiety, respectively. We investigated whether hypoxanthine-tricyclano could influence atrial inotropy and/or chronotropy, two important functions regulated by the A1 receptor, the main adenosine receptor type of the supraventricular myocardium. Paced left atria and spontaneously beating right atria, isolated from male, 30-35 weeks old, Wistar rats, were used.
View Article and Find Full Text PDFThe risk behaviors underlying the most prevalent chronic noncommunicable diseases (NCDs) encompass alcohol misuse, unhealthy diets, smoking and sedentary lifestyle behaviors. These are all linked to the altered function of the mesocorticolimbic (MCL) system. As the mesocorticolimbic circuit is central to the reward pathway and is involved in risk behaviors and mental disorders, we set out to test the hypothesis that these pathologies may be approached therapeutically as a group.
View Article and Find Full Text PDFThe receptorial responsiveness method (RRM) enables the estimation of a change in concentration of an (even degradable) agonist, near its receptor, curve fitting to (at least) two concentration-effect (E/c) curves of a stable agonist. One curve should be generated before this change, and the other afterwards, in the same system. It follows that RRM yields a surrogate parameter ("c") as the concentration of the stable agonist being equieffective with the change in concentration of the other agonist.
View Article and Find Full Text PDFCannabidiol (CBD), the most extensively studied non-intoxicating phytocannabinoid, has been attracting a lot of interest worldwide owing to its numerous beneficial effects. The aim of this study was to explore the effect that CBD exerts on the adenosinergic system of paced left atria isolated from obese type Zucker Diabetic Fatty (ZDF) rats, maintained on diabetogenic rat chow, received 60 mg/kg/day CBD or vehicle gavage for 4 weeks. We found that N6-cyclopentyladenosine (CPA), a relatively stable and poorly transported A1 adenosine receptor agonist, elicited a significantly weaker response in the CBD-treated group than in the vehicle-treated one.
View Article and Find Full Text PDFIn previous studies using isolated, paced guinea pig left atria, we observed that FSCPX, known as a selective A adenosine receptor antagonist, paradoxically increased the direct negative inotropic response to A adenosine receptor agonists (determined using concentration/effect (E/c) curves) if NBTI, a nucleoside transport inhibitor, was present. Based on mathematical modeling, we hypothesized that FSCPX blunted the cardiac interstitial adenosine accumulation in response to nucleoside transport blockade, probably by inhibiting CD39 and/or CD73, which are the two main enzymes of the interstitial adenosine production in the heart. The goal of the present study was to test this hypothesis.
View Article and Find Full Text PDFThe receptorial responsiveness method (RRM) is a procedure that is based on a simple nonlinear regression while using a model with two variables (X, Y) and (at least) one parameter to be determined (c). The model of RRM describes the co-action of two agonists that consume the same response capacity (due to the use of the same postreceptorial signaling in a biological system). While using RRM, uniquely, an acute increase in the concentration of an agonist (near the receptors) can be quantified (as c), via evaluating E/c curves that were constructed with the same or another agonist in the same system.
View Article and Find Full Text PDFIn earlier studies, we generated concentration-response (E/c) curves with CPA (-cyclopentyladenosine; a selective A adenosine receptor agonist) or adenosine, in the presence or absence of -(2-hydroxy-5-nitrobenzyl)-6-thioinosine (NBTI, a selective nucleoside transport inhibitor), and with or without a pretreatment with 8-cyclopentyl--[3-(4-(fluorosulfonyl)-benzoyloxy)propyl]--propylxanthine (FSCPX, a chemical known as a selective, irreversible A adenosine receptor antagonist), in isolated, paced guinea pig left atria. Meanwhile, we observed a paradoxical phenomenon, i.e.
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