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001-es BibID:BIBFORM074794
035-os BibID:(WoS)000447365100097 (Scopus)85052651287
Első szerző:Erdei Tamás Dániel (kísérletes farmakológus)
Cím: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 / Tamas Erdei, Adrienn Monika Szabo, Nora Lampe, Katalin Szabo, Rita Kiss, Judit Zsuga, Csaba Papp, Akos Pinter, Andras Jozsef Szentmiklosi, Zoltan Szilvassy, Bela Juhasz, Rudolf Gesztelyi
Dátum:2018
ISSN:1420-3049
Megjegyzések:Based on in silico results, recently we have assumed that FSCPX, an irreversible A1 adenosine receptor antagonist, inhibits the action of NBTI that is apparent on E/c curves of adenosine receptor agonists. As a mechanism for this unexpected effect, we hypothesized that FSCPX might modify the equilibrative and NBTI-sensitive nucleoside transporter (ENT1) in a way that it allows ENT1 to transport adenosine but impedes NBTI to inhibit this transport. This assumption implies that our method developed to estimate receptor reserve for agonists with short half-life such as adenosine, in its original form, overestimates the receptor reserve. In this study, therefore, our goals were to experimentally test our assumption on this effect of FSCPX, to improve our receptor reserve-estimating method, and then to compare the original and improved forms of this method. Thus, we improved our method and assessed the receptor reserve for the direct negative inotropic effect of adenosine with both forms of this method in guinea pig atria. We have found that FSCPX inhibits the effects of NBTI that are mediated by increasing the interstitial concentration of adenosine of endogenous (but not exogenous) origin. As a mechanism for this action of FSCPX, inhibition of enzymes participating in the interstitial adenosine production can be hypothesized, while modification of ENT1 can be excluded. Furthermore, we have shown that, in comparison with the improved form, the original version of our method overestimates receptor reserve, but only to a small extent. Nevertheless, use of the improved form is recommended in the future.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
adenosine
CPA
FSCPX
NBTI
A1 adenosine receptor
receptorial responsiveness method
atrium
Megjelenés:Molecules. - 23 : 9 (2018), p. 1-17. -
További szerzők:Szabó Adrienn Mónika (1982-) (orvos) Lampé Nóra Szabó Katalin (1989-) (táplálkozástudományi szakember) Kiss Rita (1974-) (laboratóriumi diagnosztika szakorvos) Zsuga Judit (1973-) (neurológus, pszichoterapeuta, egészségügyi szakmanager) Papp Csaba (1966-) (aneszteziológus és intenzív terápiás szakorvos) Pintér Ákos (1967-) (matematikus) Szentmiklósi József András (1948-) (farmakológus, klinikai laboratóriumi szakorvos) Szilvássy Zoltán (1957-) (belgyógyász, farmakológus, klinikai farmakológus) Juhász Béla (1978-) (kísérletes farmakológus) Gesztelyi Rudolf (1969-) (kísérletes farmakológus)
Pályázati támogatás:EFOP-3.6.2-16-2017-00015
EFOP
GINOP-2.3.2-15-2016-00043
GINOP
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
DOI
Szerző által megadott URL
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2.

001-es BibID:BIBFORM059641
035-os BibID:(WOS)000357682500005 (Scopus)84937515738
Első szerző:Pák Krisztián (gyógyszerész)
Cím:The effect of adenosine deaminase inhibition on the A1 adenosinergic and M2 muscarinergic control of contractility in eu- and hyperthyroid guinea pig atria / Krisztian Pak, Judit Zsuga, Zita Kepes, Tamas Erdei, Balazs Varga, Bela Juhasz, Andras Jozsef Szentmiklosi, Rudolf Gesztelyi
Dátum:2015
Megjegyzések:The A1 adenosine and M2 muscarinic receptors exert protective (including energy consumption limiting) effectsin the heart.We investigated the influence of adenosine deaminase (ADA) inhibition on a representative energy consumption limiting function, the direct negative inotropic effect elicited by the A1 adenosinergic and M2 muscarinergic systems, in eu- and hyperthyroid atria. Furthermore, we compared the change in the interstitial adenosine level caused by ADA inhibition and nucleoside transport blockade, two well-established processes to stimulate the cell surface A1 adenosine receptors, in both thyroid states. A classical isolated organ technique was applied supplemented with the receptorial responsiveness method (RRM), a concentration estimating procedure. Via measuring the contractile force, the direct negative inotropic capacity of N6-cyclopentyladenosine, a selectiveA1 receptor agonist, and methacholine, a muscarinic receptoragonist, was determined on the left atria isolated from 8-day solvent- and thyroxine-treated guinea pigs in the presence and absence of 2·-deoxycoformycin, a selectiveADA inhibitor, and NBTI, a selective nucleoside transporter inhibitor. We found that ADA inhibition (but not nucleoside transport blockade) increased the signal amplification of the A1 adenosinergic (but not M2 muscarinergic) system. This action of ADA inhibition developed in both thyroid states, but it was greater in hyperthyroidism. Nevertheless, ADA inhibition produced a smaller rise in the interstitial adenosine concentration than nucleoside transport blockade did in both thyroid states. Our results indicate that ADA inhibition, besides increasing the interstitial adenosine level, intensifies the atrialA1 adenosinergic function in another (thyroid hormonesensitive) way, suggesting a new mechanism of action of ADA inhibition.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Adenosine deaminase inhibition
Thyroid hormones
Heart
Atrium
Guinea pig
RRM
Megjelenés:Naunyn-Schmiedeberg's archives of pharmacology. - 388 : 8 (2015), p. 853-868. -
További szerzők:Zsuga Judit (1973-) (neurológus, pszichoterapeuta, egészségügyi szakmanager) Képes Zita (1991-) (orvos) Erdei Tamás Dániel (1992-) (kísérletes farmakológus) Varga Balázs (1984-) (kísérletes farmakológus) Juhász Béla (1978-) (kísérletes farmakológus) Szentmiklósi József András (1948-) (farmakológus, klinikai laboratóriumi szakorvos) Gesztelyi Rudolf (1969-) (kísérletes farmakológus)
Pályázati támogatás:TÁMOP-4.2.4.A/2-11-1-2012-0001
TÁMOP
TÁMOP-4.2.2.A-11/1/KONV-2012-0045
TÁMOP
Internet cím:DOI
Intézményi repozitóriumban (DEA) tárolt változat
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3.

001-es BibID:BIBFORM082554
035-os BibID:(PMID)31842299 (cikkazonosító)6264 (scopus)85076680797 (wos)000506840100158
Első szerző:Szabó Adrienn Mónika (orvos)
Cím:Accuracy and Precision of the Receptorial Responsiveness Method (RRM) in the Quantification of A1 Adenosine Receptor Agonists / Adrienn Monika Szabo, Gabor Viczjan, Tamas Erdei, Ildiko Simon, Rita Kiss, Andras Jozsef Szentmiklosi, Bela Juhasz, Csaba Papp, Judit Zsuga, Akos Pinter, Zoltan Szilvassy, Rudolf Gesztelyi
Dátum:2019
ISSN:1661-6596 1422-0067
Megjegyzések:The 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 (cx). 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 cx), via evaluating E/c curves that were constructed with the same or another agonist in the same system. As this measurement is sensitive to the implementation of the curve fitting, the goal of the present study was to test RRM by combining di erent ways and setting options, namely: individual vs. global fitting, ordinary vs. robust fitting, and three weighting options (no weighting vs. weighting by 1/Y2 vs. weighting by 1/SD2). During the testing, RRM was used to estimate the known concentrations of stable synthetic A1 adenosine receptor agonists in isolated, paced guinea pig left atria. The estimates were then compared to the known agonist concentrations (to assess the accuracy of RRM); furthermore, the 95% confidence limits of the best-fit values were also considered (to evaluate the precision of RRM). It was found that, although the global fitting o ered 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.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
A1 adenosine receptor
atrium
heart
receptorial responsiveness method
RRM
Megjelenés:International Journal Of Molecular Sciences. - 20 : 24 (2019), p. 1-14. -
További szerzők:Viczján Gábor (1993-) (kísérletes farmakológus) Erdei Tamás Dániel (1992-) (kísérletes farmakológus) Simon Ildikó (1987-) (radiográfus (BSc) Kiss Rita (1974-) (laboratóriumi diagnosztika szakorvos) Szentmiklósi József András (1948-) (farmakológus, klinikai laboratóriumi szakorvos) Juhász Béla (1978-) (kísérletes farmakológus) Papp Csaba (1966-) (aneszteziológus és intenzív terápiás szakorvos) Zsuga Judit (1973-) (neurológus, pszichoterapeuta, egészségügyi szakmanager) Pintér Ákos (1967-) (matematikus) Szilvássy Zoltán (1957-) (belgyógyász, farmakológus, klinikai farmakológus) Gesztelyi Rudolf (1969-) (kísérletes farmakológus)
Pályázati támogatás:EFOP-3.6.2-16-2017-00015
EFOP
GINOP-2.3.4-15-2016-00002
GINOP
NKFIH-1150-6/2019
Egyéb
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
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4.

001-es BibID:BIBFORM069057
035-os BibID:(cikkazonosító)839 (WoS)000404522900156 (Scopus)85020236730
Első szerző:Zsuga Judit (neurológus, pszichoterapeuta, egészségügyi szakmanager)
Cím:Methodical Challenges and a Possible Resolution in the Assessment of Receptor Reserve for Adenosine, an Agonist with Short Half-Life / Judit Zsuga, Tamas Erdei, Katalin Szabó, Nora Lampe, Csaba Papp, Akos Pinter, Andras Jozsef Szentmiklosi, Bela Juhasz, Zoltán Szilvássy, Rudolf Gesztelyi
Dátum:2017
ISSN:1420-3049
Megjegyzések:The term receptor reserve, first introduced and used in the traditional receptor theory, is an integrative measure of response-inducing ability of the interaction between an agonist and a receptor system (consisting of a receptor and its downstream signaling). The underlying phenomenon, i.e., stimulation of a submaximal fraction of receptors can apparently elicit the maximal effect (in certain cases), provides an opportunity to assess the receptor reserve. However, determining receptor reserve is challenging for agonists with short half-lives, such as adenosine. Although adenosine metabolism can be inhibited several ways (in order to prevent the rapid elimination of adenosine administered to construct concentration?effect (E/c) curves for the determination), the consequent accumulationof endogenous adenosine biases the results. To address this problem, we previously proposed a method, by means of which this bias can be mathematically corrected (utilizing a traditionalreceptor theory-independent approach). In the present investigation, we have offered in silico validation of this method by simulating E/c curves with the use of the operational model of agonism and then by evaluating them using our method. We have found that our method is suitable to reliably assess the receptor reserve for adenosine in our recently published experimental setting, suggesting that it may be capable for a qualitative determination of receptor reserve for rapidlyeliminating agonists in general. In addition, we have disclosed a possible interference between FSCPX (8-cyclopentyl-N3-[3-(4-(fluorosulfonyl)benzoyloxy)propyl]-N1-propylxanthine), an irreversible A1 adenosine receptor antagonist, and NBTI (S-(2-hydroxy-5-nitrobenzyl)-6-thioinosine), a nucleoside transport inhibitor, i.e., FSCPX may blunt the effect of NBTI.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
adenozin
szív
A1 adenozin receptor
pitvar
RRM
receptor rezerv
Megjelenés:Molecules. - 22 : 5 (2017), p. 1-17. -
További szerzők:Erdei Tamás Dániel (1992-) (kísérletes farmakológus) Szabó Katalin (1989-) (táplálkozástudományi szakember) Lampé Nóra Papp Csaba (1966-) (aneszteziológus és intenzív terápiás szakorvos) Pintér Ákos (1967-) (matematikus) Szentmiklósi József András (1948-) (farmakológus, klinikai laboratóriumi szakorvos) Juhász Béla (szülész-nőgyógyász) Szilvássy Zoltán (1957-) (belgyógyász, farmakológus, klinikai farmakológus) Gesztelyi Rudolf (1969-) (kísérletes farmakológus)
Pályázati támogatás:EFOP-3.6.2-16-2017-00015
Egyéb
Internet cím:DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
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