TY - JOUR AU - Le, Y. AU - Lu, D. AU - Xue, M. TI - Purinergic signaling in thyroid disease JF - PURINERGIC SIGNALLING J2 - PURINERG SIGNAL VL - 19 PY - 2022 IS - 1 SP - 221 EP - 227 PG - 7 SN - 1573-9538 DO - 10.1007/s11302-022-09858-2 UR - https://m2.mtmt.hu/api/publication/32837575 ID - 32837575 N1 - Department of Endocrinology and Metabolism, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Guangdong, Shenzhen, 518020, China Department of Endocrinology, Peking University Shenzhen Hospital, Guangdong, Shenzhen, 518036, China Cited By :1 Export Date: 21 June 2023 Correspondence Address: Xue, M.; Department of Endocrinology and Metabolism, Guangdong, China; email: xue.meng@szhospital.com Chemicals/CAS: adenosine triphosphate, 15237-44-2, 56-65-5, 987-65-5; adenosine, 58-61-7; Adenosine; Nucleotides Funding details: National Natural Science Foundation of China, NSFC, NNSF, NNSFC, 81900738 Funding text 1: This work was supported by grants from the National Natural Science Foundations of China (grant numbers 81900738). AB - It is known that thyroid hormones play pivotal roles in a wide variety of pathological and physiological events. Thyroid diseases, mainly including hyperthyroidism, hypothyroidism, and thyroid cancer, are highly prevalent worldwide health problems and frequently associated with severe clinical manifestations. However, etiology of hyperthyroidism, hypothyroidism, and thyroid cancer is not fully understood. Purinergic signaling accounts for a complex network of receptors and extracellular enzymes responsible for the recognition and degradation of extracellular nucleotides and adenosine. It has been established that purinergic signaling modulates pathways in a wide range of physiopathological conditions including hypertension, diabetes, hepatic diseases, psychiatric and neurodegeneration, rheumatic immune diseases, and cancer. More recently, the purinergic system is found to exist in thyroid gland and play an important role in the pathophysiology of thyroid diseases. Therefore, throughout this review, we focus on elaborating the changes in purinergic receptors, extracellular enzymes, and extracellular nucleotides and adenosine in hyperthyroidism, hypothyroidism, and thyroid cancer. Profound understanding of the relationship between the purinergic signaling with thyroid diseases provides a promising research area for insights into the molecular basis of thyroid diseases and also develops new and exciting insights into the treatment of thyroid diseases, especially thyroid cancer. © 2022, The Author(s), under exclusive licence to Springer Nature B.V. LA - English DB - MTMT ER - TY - JOUR AU - Viczján, Gábor AU - Erdei, Tamás Dániel AU - Óvári, Ignác AU - Lampé, Nóra AU - Szekeres, Réka Mária AU - Bombicz, Mariann AU - Takács, Barbara AU - Szilágyi, Anna AU - Zsuga, Judit AU - Szilvássy, Zoltán AU - Juhász, Béla AU - Gesztelyi, Rudolf TI - 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 JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 22 PY - 2021 IS - 18 PG - 21 SN - 1661-6596 DO - 10.3390/ijms22189831 UR - https://m2.mtmt.hu/api/publication/32193722 ID - 32193722 AB - In previous studies using isolated, paced guinea pig left atria, we observed that FSCPX, known as a selective A(1) adenosine receptor antagonist, paradoxically increased the direct negative inotropic response to A(1) 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. In vitro CD39 and CD73 inhibitor assays were carried out; furthermore, E/c curves were constructed in isolated, paced rat and guinea pig left atria using adenosine, CHA and CPA (two A(1) adenosine receptor agonists), FSCPX, NBTI and NBMPR (two nucleoside transport inhibitors), and PSB-12379 (a CD73 inhibitor), measuring the contractile force. We found that FSCPX did not show any inhibitory effect during the in vitro enzyme assays. However, we successfully reproduced the paradox effect of FSCPX in the rat model, mimicked the "paradox" effect of FSCPX with PSB-12379, and demonstrated the lipophilia of FSCPX, which could explain the negative outcome of inhibitor assays with CD39 and CD73 dissolved in a water-based solution. Taken together, these three pieces of indirect evidence are strong enough to indicate that FSCPX possesses an additional action besides the A(1) adenosine receptor antagonism, which action may be the inhibition of an ectonucleotidase. Incidentally, we found that POM-1 inhibited CD73, in addition to CD39. LA - English DB - MTMT ER - TY - JOUR AU - Vargáné Szabó, Adrienn Mónika AU - Viczján, Gábor AU - Erdei, Tamás Dániel AU - Simon, Ildiko AU - Kiss, Rita AU - Szentmiklósi, József András AU - Juhász, Béla AU - Papp, Csaba Sándor AU - Zsuga, Judit AU - Pinter, Akos AU - Szilvassy, Zoltan AU - Gesztelyi, Rudolf TI - Accuracy and Precision of the Receptorial Responsiveness Method (RRM) in the Quantification of A1 Adenosine Receptor Agonists JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 20 PY - 2019 IS - 24 PG - 14 SN - 1661-6596 DO - 10.3390/ijms20246264 UR - https://m2.mtmt.hu/api/publication/31012994 ID - 31012994 LA - English DB - MTMT ER - TY - JOUR AU - Erdei, Tamás Dániel AU - Vargáné Szabó, Adrienn Mónika AU - Lampé, Nóra AU - Szabo, K AU - Kiss, Rita AU - Zsuga, Judit AU - Papp, Csaba Sándor AU - Pintér, Ákos AU - Szentmiklósi, József András AU - Szilvassy, Z AU - Juhász, Béla AU - Gesztelyi, Rudolf TI - 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 JF - MOLECULES J2 - MOLECULES VL - 23 PY - 2018 IS - 9 PG - 17 SN - 1420-3049 DO - 10.3390/molecules23092186 UR - https://m2.mtmt.hu/api/publication/3407995 ID - 3407995 LA - English DB - MTMT ER - TY - JOUR AU - Zsuga, Judit AU - Erdei, Tamás Dániel AU - Szabo, K AU - Lampé, Nóra AU - Papp, Csaba Sándor AU - Pintér, Ákos AU - Szentmiklósi, József András AU - Juhász, Béla AU - Szilvássy, Zoltán AU - Gesztelyi, Rudolf TI - Methodical Challenges and a Possible Resolution in the Assessment of Receptor Reserve for Adenosine, an Agonist with Short Half-Life JF - MOLECULES J2 - MOLECULES VL - 22 PY - 2017 IS - 5 PG - 17 SN - 1420-3049 DO - 10.3390/molecules22050839 UR - https://m2.mtmt.hu/api/publication/3224927 ID - 3224927 N1 - Támogatás: A HU-MATHS-IN – Magyar Ipari Innovációs Matematikai Szolgáltatási Hálózat tevékenységének elmélyítése (EFOP-3.6.2-16-2017-00015) LA - English DB - MTMT ER - TY - JOUR AU - Hughes, SJ AU - Cravetchi, X AU - Vilas, G AU - Hammond, JR TI - Adenosine A1 receptor activation modulates human equilibrative nucleoside transporter 1 (hENT1) activity via PKC-mediated phosphorylation of serine-281 JF - CELLULAR SIGNALLING J2 - CELL SIGNAL VL - 27 PY - 2015 IS - 5 SP - 1008 EP - 1018 PG - 11 SN - 0898-6568 DO - 10.1016/j.cellsig.2015.02.023 UR - https://m2.mtmt.hu/api/publication/24573133 ID - 24573133 LA - English DB - MTMT ER - TY - JOUR AU - Pák, Krisztián AU - Zsuga, Judit AU - Képes, Zita AU - Erdei, Tamás Dániel AU - Varga, Balázs AU - Juhász, Béla AU - Szentmiklósi, József András AU - Gesztelyi, Rudolf TI - The effect of adenosine deaminase inhibition on the A1 adenosinergic and M2 muscarinergic control of contractility in eu- and hyperthyroid guinea pig atria JF - NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY J2 - N-S ARCH PHARMACOL VL - 388 PY - 2015 IS - 8 SP - 853 EP - 868 PG - 16 SN - 0028-1298 DO - 10.1007/s00210-015-1121-6 UR - https://m2.mtmt.hu/api/publication/2883644 ID - 2883644 N1 - 215420 LA - English DB - MTMT ER - TY - JOUR AU - Pák, Krisztián AU - Papp, Csaba Sándor AU - Galajda, Z AU - Szerafin, Tamás AU - Varga, Balázs AU - Juhász, Béla AU - Haines, David AU - Szentmiklósi, József András AU - Tósaki, Árpád AU - Gesztelyi, Rudolf TI - Approximation of A1 adenosine receptor reserve appertaining to the direct negative inotropic effect of adenosine in hyperthyroid guinea pig left atria JF - GENERAL PHYSIOLOGY AND BIOPHYSICS J2 - GEN PHYSIOL BIOPHYS VL - 33 PY - 2014 IS - 2 SP - 177 EP - 188 PG - 12 SN - 0231-5882 DO - 10.4149/gpb_2013079 UR - https://m2.mtmt.hu/api/publication/2441369 ID - 2441369 LA - English DB - MTMT ER - TY - JOUR AU - Pák, Krisztián AU - Kiss, Z AU - Erdei, Tamás Dániel AU - Képes, Zita AU - Gesztelyi, Rudolf TI - Új lehetőség farmakológiai agonisták receptorközeli koncentrációjának becslésére: a receptoriális válaszkészség módszer (RRM) JF - ACTA PHARMACEUTICA HUNGARICA J2 - ACTA PHARM HUNG VL - 84 PY - 2014 IS - 1 SP - 38 EP - 52 PG - 15 SN - 0001-6659 UR - https://m2.mtmt.hu/api/publication/25422883 ID - 25422883 N1 - 190433 AB - Cardiovascular disease is the biggest challenge in terms of life expectancy in developed countries. Adenosine contributes to the adaptation of the heart to ischemia and hypoxia, because adenosine, in addition to its metabolite role in the nucleic acid metabolism, is the endogenous agonist of the ubiquitous adenosine receptor family. Adenosine receptor activation is beneficial in most cases, it improves the balance between energy supply and consumption, reduces injury caused by stressors and inhibits the unfavorable tissue remodeling. Pharmacological manipulation of cardioprotective effects evoked by adenosine is an important, although to date not sufficiently utilized endeavor that may have therapeutic and preventive implications in cardiovascular diseases. As the ligand binding site of adenosine receptors is accessible from the extracellular space, it is especially important to know the adenosine concentration of the interstitial fluid ([Ado]ISF). However, in the functioning heart, [Ado]ISF values range in an extremely wide interval, spanning from nano- to micromolar concentrations, as estimated by the commonly used methods. Our recently developed procedure, the receptorial responsiveness method (RRM), may resolve this problem in certain cases. RRM enables quantification of an acute increase in the concentration of a pharmacological agonist, uniquely in the microenvironment of the receptors of the given agonist. As a limitation, concentration of agonists with short half-life (just like adenosine) at their receptors can only be quantified with the equieffective concentration of a stable agonist exerting the same action. In a previous study using RRM, inhibition of the transmembrane nucleoside transport in the euthyroid guinea pig atrium produced an increase in [Ado]ISF that was equieffective with 18.8 ± 3 nM CPA (N6-cyclopentyladenosine, a stable, selective A1 adenosine receptor agonist). This finding is consistent with observations of others, i.e., in the normoxic heart, adenosine flow is directed into the cell interior, and thus transport blockade elevates the extracellular adenosine level. In turn, nucleoside transport inhibition in the hyperthyroid guinea pig atrium caused a rise in [Ado]ISF equieffective with 46.5 ± 13.7 nM CPA. In sum, our work team was the first to demonstrate that adenosine transport in the hyperthyroid atrium has the same direction but is more intense as/than that in the euthyroid one. LA - Hungarian DB - MTMT ER - TY - JOUR AU - Kiss, Zsuzsanna Mária AU - Pák, Krisztián AU - Zsuga, Judit AU - Juhász, Béla AU - Varga, Balázs AU - Szentmiklósi, József András AU - Haines, David AU - Tósaki, Árpád AU - Gesztelyi, Rudolf TI - The guinea pig atrial A1 adenosine receptor reserve for the direct negative inotropic effect of adenosine JF - GENERAL PHYSIOLOGY AND BIOPHYSICS J2 - GEN PHYSIOL BIOPHYS VL - 32 PY - 2013 IS - 3 SP - 325 EP - 335 PG - 11 SN - 0231-5882 DO - 10.4149/gpb_2013041 UR - https://m2.mtmt.hu/api/publication/2360355 ID - 2360355 LA - English DB - MTMT ER - TY - THES AU - Kiss, Zsuzsanna Mária TI - Az A1 adenozin receptor tiroxinnal szembeni érzékenységének és a direkt negatív inotróp hatáshoz tartozó receptor rezervjének meghatározása tengerimalac pitvaron PY - 2013 SP - 110 UR - https://m2.mtmt.hu/api/publication/25250675 ID - 25250675 N1 - Tudományág: gyógyszerészeti tudományok A védés időpontja: 2013-10-02 13:00 A fokozat odaítélésének dátuma: 2013-11-13 AB - Első vizsgálati modellünk eredményei szerint a tengerimalac pitvari A1 receptor CPX (szelektív, ortoszterikus A1 receptor antagonista) iránti affinitása hyperthyreosisban kismértékben csökken az euthyreoid állapothoz képest. A kötőhely affinitáscsökkenése hozzájárulhat az A1 receptor mediálta folyamatok jól ismert gyengüléséhez hyperthyreoid állapotban, a mérték alapján azonban valószínű, hogy ez a mechanizmus csak részben felelős a jelenségért. Azt is megállapítottuk, hogy a CPX nem csak az eu-, hanem a hyperthyreoid pitvari A1 receptoron is tisztán kompetitív antagonista. Második vizsgálati modell kísérletei során azt kaptuk, hogy az irreverzibilis A1 receptor antagonista FSCPX (10 µM 45 percig, majd 75 perc mosás) nem csökkentette olyan mértékben a működőképes A1 receptorok számát, ami miatt szignifikánsan csökkenne a vizsgált A1 receptor full agonisták (NECA, CPA, CHA és adenozin) által kiváltott direkt negatív inotróp hatás maximuma tengerimalac bal pitvaron. Ezzel összhangban a stabil, szintetikus A1 receptor full agonisták (NECA, CPA, CHA) esetén a közel maximális direkt negatív inotróp hatáshoz tartozó A1 receptor rezervre igen nagy, 80-92% közötti értékeket kaptunk. Ezek a receptor rezerv értékek nagyobbak voltak minden korábbi irodalmi adatnál, ami az A1 receptor mediálta egyéb hatásokra vonatkozott tengerimalac pitvaron. Az élő szövetben bomlékony és gyorsan kompartmentalizálódó adenozin esetében az A1 receptor rezerv kvantifikálása nem sikerült, sőt az adenozin E/c görbék paradox módon viselkedtek NBTI (az adenozin intracelluláris eliminációját kivédő nukleozid transzport gátló) jelenlétében. Az NBTI miatt torzult adenozin E/c görbék matematikai korrekciója után azonban kiderült, hogy az adenozin direkt negatív inotróp hatására vonatkozó A1 receptor rezerv a szintetikus agonistákéhoz hasonlóan nagy. Ezek az eredményeink arra utalnak, hogy a pitvari kontraktilitás igen érzékeny az A1 receptor stimulációjára, ami miatt számítani kell a pitvari kontrakciós erő csökkenésére parciális A1 receptor agonisták és A1 receptor enhancer-ek esetében is, mint lehetséges mellékhatásra. The main finding of our first study is that affinity of the guinea pig atrial A1 receptor towards CPX, a selective, orthosteric A1 receptor antagonist, moderately decreases in hyperthyroidism as compared to the euthyroid state. The reduced affinity of the binding site may contribute to the well-known decrease of A1 receptor mediated actions in hyperthyroidism (although it is probable that this mechanism is only in part responsible for the phenomenon). In addition, we found that CPX is a pure competitive antagonist for the hyperthyroid and not only for the euthyroid atrial A1 receptor. Results of our second study show that FSCPX, an irreversible A1 receptor antagonist (used in 10 µM for 45 min, followed by 75 min wash-out), failed to decrease the number of operable A1 receptors in an extent that would be sufficient to significantly reduce the maximum of the direct negative inotropic effect of NECA, CPA, CHA and adenosine, four A1 receptor full agonists, in guinea pig left atria. Accordingly, A1 receptor reserve has been found to be considerably great, ranging between 80-92% for the near maximal direct negative inotropic effect evoked by NECA, CPA and CHA, three stable synthetic A1 receptor full agonists. These receptor reserve values are higher than all historical values determined for any other A1 receptor mediated effect in the guinea pig atrium. Quantification of A1 receptor reserve failed for adenosine, a compound that is eliminated and compartmentalizes rapidly in the living tissues. Moreover, adenosine E/c curves generated in the presence of NBTI, a nucleoside transport inhibitor preventing the intracellular elimination of adenosine, seemed to behave paradoxically. However, after the mathematical correction of adenosine E/c curves biased by NBTI, it turned out that A1 receptor reserve for the direct negative inotropic effect of adenosine is similarly great as that of the synthetic agonists. These results indicate that atrial contractility is very sensitive to the stimulation of A1 receptors. Thus, a decrease in the contractile force of atria, as a possible side effect, should be considered even in the case of partial A1 receptor agonists and A1 receptor enhancers. LA - English DB - MTMT ER - TY - JOUR AU - Gesztelyi, Rudolf AU - Kiss, Z AU - Zsuga, Judit AU - Pák, Krisztián AU - Papp, Csaba Sándor AU - Galajda, Zoltán AU - Branzaniuc, K AU - Szentmiklósi, József András AU - Tósaki, Árpád TI - Thyroid hormones decrease the affinity of 8-cyclopentyl-1,3-dipropylxanthine (CPX), a competitive antagonist, for the guinea pig atrial A1 adenosine receptor JF - GENERAL PHYSIOLOGY AND BIOPHYSICS J2 - GEN PHYSIOL BIOPHYS VL - 31 PY - 2012 IS - 4 SP - 389 EP - 400 PG - 12 SN - 0231-5882 DO - 10.4149/gpb_2012_043 UR - https://m2.mtmt.hu/api/publication/2128687 ID - 2128687 LA - English DB - MTMT ER - TY - THES AU - Grenczer, M TI - A receptoriális válaszkészség módszer (RRM) hasznosíthatósága és megbízhatósága, különös tekintettel az agonisták és a biológiai rendszer tulajdonságainak befolyására PY - 2011 UR - https://m2.mtmt.hu/api/publication/23119512 ID - 23119512 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Grenczer, Mária AU - Zsuga, Judit AU - Majoros, László AU - Pintér, Ákos AU - Kemény-Beke, Ádám AU - Juhász, Béla AU - Tósaki, Árpád AU - Gesztelyi, Rudolf TI - Effect of asymmetry of concentration-response curves on the results obtained by the receptorial responsiveness method (RRM). an in silico study TS - an in silico study JF - CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY J2 - CAN J PHYSIOL PHARM VL - 88 PY - 2010 IS - 11 SP - 1074 EP - 1083 PG - 10 SN - 0008-4212 DO - 10.1139/Y10-089 UR - https://m2.mtmt.hu/api/publication/1395017 ID - 1395017 LA - English DB - MTMT ER - TY - JOUR AU - Grenczer, Mária AU - Pintér, Ákos AU - Zsuga, Judit AU - Kemény-Beke, Ádám AU - Juhász, Béla AU - Szodoray, P AU - Tósaki, Árpád AU - Gesztelyi, Rudolf TI - The influence of affinity, efficacy, and slope factor on the estimates obtained by the receptorial responsiveness method (RRM). a computer simulation study TS - a computer simulation study JF - CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY J2 - CAN J PHYSIOL PHARM VL - 88 PY - 2010 IS - 11 SP - 1061 EP - 1073 PG - 13 SN - 0008-4212 DO - 10.1139/Y10-078 UR - https://m2.mtmt.hu/api/publication/1395027 ID - 1395027 LA - English DB - MTMT ER - TY - CHAP AU - Juhász, Béla AU - Gesztelyi, Rudolf AU - Tósaki, Árpád ED - Dipak, K Das TI - Some useful methods for the detection of redox signaling in various organs T2 - Methods in Redox Signaling PB - Mary Ann Liebert CY - New Rochelle (NY) SN - 9781934854068 PY - 2010 SP - 163 EP - 171 PG - 9 UR - https://m2.mtmt.hu/api/publication/1254050 ID - 1254050 LA - English DB - MTMT ER - TY - JOUR AU - Zsuga, Judit TI - Az aszimmetrikus dimetil-arginin (adma) mint kapocs az inzulinrezisztencia és az atherosclerosis között [Asymmetric dimethil-arginine (ADMA) as a link between insulin resistance and atherosclerosis] JF - IDEGGYOGYASZATI SZEMLE / CLINICAL NEUROSCIENCE J2 - IDEGGYOGY SZEMLE VL - 61 PY - 2008 IS - 5-6 SP - 183 EP - 192 PG - 10 SN - 0019-1442 UR - https://m2.mtmt.hu/api/publication/2057566 ID - 2057566 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Kemény-Beke, Ádám AU - Jakab, A AU - Zsuga, Judit AU - Vecsernyés, Miklós AU - Karsai, D AU - Pasztor, F AU - Grenczer, Mária AU - Szentmiklósi, József András AU - Berta, András AU - Gesztelyi, Rudolf TI - Adenosine deaminase inhibition enhances the inotropic response mediated by A(1) adenosine receptor in hyperthyroid guinea pig atrium JF - PHARMACOLOGICAL RESEARCH J2 - PHARMACOL RES VL - 56 PY - 2007 IS - 2 SP - 124 EP - 131 PG - 8 SN - 1043-6618 DO - 10.1016/j.phrs.2007.04.017 UR - https://m2.mtmt.hu/api/publication/1191395 ID - 1191395 LA - English DB - MTMT ER -