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
Abstract
:1. Introduction
2. Results
2.1. CD39 and CD73 Inhibitor Assays
2.2. Interaction of FSCPX with NBMPR in the Rat Left Atrium
2.2.1. Response to Adenosine before Any In Vitro Treatment
2.2.2. Response to CHA in the Control Groups
2.2.3. Response to CHA after Different In Vitro Treatments
2.3. Interaction of PSB-12379 with NBTI in the Guinea Pig Left Atrium
2.3.1. Response to Adenosine in All Groups
2.3.2. Response to CPA in the Groups Labeled with “for CPA”
2.3.3. Response to Adenosine in the Groups Labeled with “for Ado”
2.4. The Influence of Different Administration Regimens on the Effect of FSCPX in Rat and Guinea Pig Left Atria
2.4.1. Response to Adenosine before Any In Vitro Treatment
2.4.2. Response to CPA after an In Vitro Pretreatment with 10 μM FSCPX Using Different Administration Regimens
3. Discussion
4. Materials and Methods
4.1. In Vitro Enzyme Inhibitor Assays
4.1.1. Materials
4.1.2. Protocol
4.2. Ex Vivo Functional Assays
4.2.1. Materials
4.2.2. Animals and Groups
4.2.3. Protocols
4.2.4. Characterization of the E/c Curves
4.2.5. Data Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Ectonucleotidases | |||
ecto-nucleoside 5′-triphosphate diphosphohydrolase family (E-NTPDases) a.k.a. ecto-apyrases | |||
group E-NTPDase1–4 | |||
E-NTPDase1 a.k.a. lymphocyte surface protein CD39 a.k.a. ecto-apyrase CD39 | |||
E-NTPDase2 a.k.a. ecto-ATPase CD39L1 | |||
E-NTPDase3 a.k.a. HB6 | |||
E-NTPDase4: UDPase and LALP70 | |||
group E-NTPDase5,6 | |||
E-NTPDase5 a.k.a. CD39L4 | |||
E-NTPDase6 (?) | |||
ectonucleotide pyrophosphatase/phosphodiesterase family (E-NPP family) a.k.a. ecto-phosphodiesterase/pyrophosphatase family a.k.a. PC-1 family a.k.a. phosphodiesterase/nucleotide pyrophosphatase (PDNP) family | |||
murine plasma cell differentiation antigen NPP1 (PC-1) | |||
murine plasma cell differentiation antigen NPP2 (PD-Iα and autotaxin) | |||
murine plasma cell differentiation antigen NPP3 (PD-Iβ a.k.a. B10 a.k.a. gp130RB13-6) | |||
alkaline phosphatases a.k.a. non-specific ecto-phosphomonoesterases | |||
lymphocyte surface protein CD73 a.k.a. ecto-5′-nucleotidase |
DMSO (5 Cycles) | FSCPX (1 Cycle) | FSCPX (2 Cycles) | FSCPX (5 Cycles) | ||
---|---|---|---|---|---|
R-i | Emax (%) | 47.65 | 54.15 | 54.53 | 57.1 |
(45.08 to 50.57) | (47.92 to 64.04) | (48.41 to 65.63) | (49.92 to 73.19) | ||
logEC50 | −6.956 | −5.558 | −5.17 | −5.123 | |
(−7.105 to −6.788) | (−5.809 to −5.209) | (−5.391 to −4.812) | (−5.346 to −4.689) | ||
n | 0.797 | 0.739 | 0.68 | 0.815 | |
(0.632 to 1.046) | (0.547 to 1.006) | (0.533 to 0.852) | (0.567 to 1.136) | ||
r2 | 0.9474 | 0.9285 | 0.9526 | 0.9261 | |
R-g | Emax (%) | 49.99 | |||
(47.96 to 52.23) | |||||
logEC50 | −6.879 | −5.693 | −5.311 | −5.313 | |
(−7.019 to −6.73) | (−5.836 to −5.548) | (−5.45 to −5.173) | (−5.446 to −5.181) | ||
n | 0.814 | ||||
(0.719 to 0.926) | |||||
r2 | 0.9431 | 0.9261 | 0.9505 | 0.9161 | |
GP-i | Emax (%) | 93.41 | 93.92 | 95.78 | 96.2 |
(89.19 to 97.92) | (89.71 to 98.72) | (90.73 to 101.9) | (91.4 to 101.9) | ||
logEC50 | −7.319 | −6.224 | −6.028 | −5.886 | |
(−7.457 to −7.18) | (−6.326 to −6.113) | (−6.148 to −5.891) | (−5.994 to −5.762) | ||
n | 0.819 | 0.852 | 0.745 | 0.745 | |
(0.666 to 1.02) | (0.711 to 1.026) | (0.626 to 0.894) | (0.636 to 0.878) | ||
r2 | 0.9618 | 0.9829 | 0.9789 | 0.9812 | |
GP-g | Emax (%) | 94.35 | |||
(92.15 to 96.67) | |||||
logEC50 | −7.303 | −6.218 | −6.052 | −5.917 | |
(−7.398 to −7.209) | (−6.316 to −6.119) | (−6.146 to −5.958) | (−6.005 to −5.828) | ||
n | 0.794 | ||||
(0.727 to 0.869) | |||||
r2 | 0.9616 | 0.9826 | 0.9787 | 0.981 |
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Viczjan, G.; Erdei, T.; Ovari, I.; Lampe, N.; Szekeres, R.; Bombicz, M.; Takacs, B.; Szilagyi, A.; Zsuga, J.; Szilvassy, Z.; et al. 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. Int. J. Mol. Sci. 2021, 22, 9831. https://doi.org/10.3390/ijms22189831
Viczjan G, Erdei T, Ovari I, Lampe N, Szekeres R, Bombicz M, Takacs B, Szilagyi A, Zsuga J, Szilvassy Z, et al. 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. International Journal of Molecular Sciences. 2021; 22(18):9831. https://doi.org/10.3390/ijms22189831
Chicago/Turabian StyleViczjan, Gabor, Tamas Erdei, Ignac Ovari, Nora Lampe, Reka Szekeres, Mariann Bombicz, Barbara Takacs, Anna Szilagyi, Judit Zsuga, Zoltan Szilvassy, and et al. 2021. "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" International Journal of Molecular Sciences 22, no. 18: 9831. https://doi.org/10.3390/ijms22189831