The surmountable effect of FSCPX, an irreversible A1 adenosine receptor antagonist, on the negative inotropic action of A1 adenosine receptor full agonists in isolated guinea pig left atria

@article{Gesztelyi2013TheSE,
  title={The surmountable effect of FSCPX, an irreversible A1 adenosine receptor antagonist, on the negative inotropic action of A1 adenosine receptor full agonists in isolated guinea pig left atria},
  author={Rudolf Gesztelyi and Zs. Csap{\'o}n{\'e} Kiss and Zita Wachal and B{\'e}la Juh{\'a}sz and Mariann Bombicz and Evelin Csepanyi and Kriszti{\'a}n P{\'a}k and Judit Zsuga and Csaba Papp and Zolt{\'a}n Galajda and Klara Brănzaniuc and R{\'o}bert P{\'o}rsz{\'a}sz and Andr{\'a}s J{\'o}zsef Szentmikl{\'o}si and {\'A}rp{\'a}d T{\'o}saki},
  journal={Archives of Pharmacal Research},
  year={2013},
  volume={36},
  pages={293-305}
}
A1 adenosine receptors (A1 receptors) are widely expressed in mammalian tissues; therefore attaining proper tissue selectivity is a cornerstone of drug development. The fact that partial agonists chiefly act on tissues with great receptor reserve can be exploited to achieve an appropriate degree of tissue selectivity. To the best of our knowledge, the A1 receptor reserve has not been yet quantified for the atrial contractility. A1 receptor reserve was determined for the direct negative… Expand
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14 Citations
Background Citations
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Methods Citations
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Results Citations
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14 Citations

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The guinea pig atrial A1 adenosine receptor reserve for the direct negative inotropic effect of adenosine.
TLDR
The corrected curves indicate a substantial A1 receptor reserve for the direct negative inotropy evoked by adenosine and suggest that accumulation of an endogenous agonist may bias the E/c curve constructed with the same or similar agonist that can lead to seemingly paradoxical results. Expand
Approximation of A1 adenosine receptor reserve appertaining to the direct negative inotropic effect of adenosine in hyperthyroid guinea pig left atria.
TLDR
Thyroxine treatment does not substantially affect the A1 receptor reserve for the direct negative inotropic effect of adenosine, demonstrating that the most probable adverse effect affecting the heart may be a decrease of atrial contractility in both eu- and hyperthyroid conditions. Expand
A Body of Circumstantial Evidence for the Irreversible Ectonucleotidase Inhibitory Action of FSCPX, an Agent Known as a Selective Irreversible A1 Adenosine Receptor Antagonist So Far
TLDR
Three pieces of indirect evidence are strong enough to indicate that FSCPX possesses an additional action besides the A1 adenosine receptor antagonism, which action may be the inhibition of an ectonucleotidase. Expand
FSCPX, a Chemical Widely Used as an Irreversible A1 Adenosine Receptor Antagonist, Modifies the Effect of NBTI, a Nucleoside Transport Inhibitor, by Reducing the Interstitial Adenosine Level in the Guinea Pig Atrium
TLDR
It is found that FSCPX inhibits the effects of NBTI that are mediated by increasing the interstitial concentration of adenosine of endogenous (but not exogenous) origin, and the original version of the receptor reserve-estimating method overestimates receptor reserve but only to a small extent. Expand
A1 Adenosine Receptor–Mediated Inhibition of Parasympathetic Neuromuscular Transmission in Human and Murine Urinary Bladder
TLDR
Amplitudes of the P2X purinoceptor–mediated excitatory junctional potentials (EJPs) recorded with intracellular microelectrodes were reduced in amplitude by CPA and adenosine with no effect on the spontaneous EJP amplitudes, confirming the prejunctional action of these agents. Expand
Methodical Challenges and a Possible Resolution in the Assessment of Receptor Reserve for Adenosine, an Agonist with Short Half-Life
TLDR
The method proposed is suitable to reliably assess the receptor reserve for adenosine in the recently published experimental setting, suggesting that it may be capable for a qualitative determination of receptors reserve for rapidly eliminating agonists in general. Expand
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
TLDR
In silico evidence is obtained for an interference between effects of FSCPX and NBTI upon the authors' ex vivo experimental setting, and the mechanism of this interference is hypothesized to be an enzyme participating in the interstitial adenosine formation. Expand
Ion Fluxes through KCa2 (SK) and Cav1 (L-type) Channels Contribute to Chronoselectivity of Adenosine A1 Receptor-Mediated Actions in Spontaneously Beating Rat Atria
TLDR
Functional data indicate that while both A1 and M2 receptors favor the opening of GIRK/KIR3.1/3.4 channels modulating atrial chronotropy, A1 receptors may additionally restrain KCa2/SK activation thereby compensating atrial inotropic depression by increasing the time available for Ca2+ influx through Cav1 (L-type) channels. Expand
Molecular probes for the human adenosine receptors
TLDR
This review summarizes applications of covalent or reversible probes in GPCR research, and serves as an invitation to walk another mile to further improve probe characteristics and develop additional tags that allow the investigation of adenosine receptors and other GPCRs in even finer detail. Expand
Accuracy and Precision of the Receptorial Responsiveness Method (RRM) in the Quantification of A1 Adenosine Receptor Agonists
TLDR
It was found that, although the global fitting offered the most convenient way to perform RRM, the best estimates were provided by the individual fitting without any weighting, almost irrespective of the fact whether ordinary or robust fitting was chosen. Expand
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