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001-es BibID:BIBFORM030264
035-os BibID:WOS:000086138300017
Első szerző:Nánási Péter Pál (élettanász)
Cím:Biphasic effect of bimoclomol on calcium handling in mammalian ventricular myocardium / Péter P. Nánási, Sándor Sárközi, Gyula Szigeti, István Jóna, Csaba Szegedi, Ágnes Szabó, Tamás Bányász, János Magyar, Péter Szigligeti, Ágnes Körtvély, László Csernoch, László Kovács, Andrea Jednákovits
Dátum:2000
ISSN:0007-1188
Megjegyzések:1 Concentration-dependent effects of bimoclomol, the novel heat shock protein coinducer, on intracellular calcium transients and contractility were studied in Langendorff-perfused guinea-pig hearts loaded with the fluorescent calcium indicator dye Fura-2. Bimoclomol had a biphasic effect on contractility: both peak left ventricular pressure and the rate of force development significantly increased at a concentration of 10 nM or higher. The maximal effect was observed between 0.1 and 1 mu M, and the positive inotropic action disappeared by further increasing the concentration of bimoclomol. The drug increased systolic calcium concentration with a similar concentration-dependence. In contrast, diastolic calcium concentration increased monotonically in the presence of bimoclomol. Thus low concentrations of the drug (10-100 nM) increased, whereas high concentrations (10 mu M) decreased the amplitude of intracellular calcium transients. 2 Effects of bimoclomol on action potential configuration was studied in isolated canine ventricular myocytes. Action potential duration was increased at low (10 nM), unaffected at intermediate (0.1-1 mu M) and decreased at high (10-100 mu M) concentrations of the drug. 3 In single canine sarcoplasmic calcium release channels (ryanodine receptor), incorporated into artificial lipid bilayer, bimoclomol significantly increased the open probability of the channel in the concentration range of 1-10 mu M. The increased open probability was associated with increased mean open time. The effect of bimoclomol was again biphasic: the open probability decreased below the control level in the presence of 1 mM bimoclomol. 4 Bimoclomol (10 mu M-1 mM) had no significant effect on the rate of calcium uptake into sarcoplasmic reticulum vesicles of the dog, indicating that in vivo calcium reuptake might not substantially be affected by the drug. 5 In conclusion, the positive inotropic action of bimoclomol is likely due to the activation of the sarcoplasmic reticulum calcium release channel in mammalian ventricular myocardium.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:British Journal of Pharmacology. - 129 : 7 (2000), p. 1405-1412. -
További szerzők:Sárközi Sándor (1966-) (élettanász) Szigeti Gyula (1969-) (élettanász, elektrofiziológus) Jóna István (1948-) (élettanász, fizikus) Szegedi Csaba Szabó Ágnes Bányász Tamás (1960-) (élettanász) Magyar János (1961-) (élettanász) Szigligeti Péter Körtvély Ágnes Csernoch László (1961-) (élettanász) Kovács László (1939-) (élettanász) Jednákovits Andrea
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001-es BibID:BIBFORM030247
Első szerző:Szentandrássy Norbert (élettanász)
Cím:Effect of thymol on calcium handling in mammalian ventricular myocardium / Norbert Szentandrássy, Gyula Szigeti, Csaba Szegedi, Sándor Sárközi, János Magyar, Tamás Bányász, László Csernoch, László Kovács, Péter P. Nánási, István Jóna
Dátum:2004
ISSN:0024-3205
Megjegyzések:Concentration-dependent effects of thymol on calcium handling were studied in canine and guinea pig cardiac preparations (Langendorff-perfused guinea pig hearts, canine ventricular trabeculae, canine sarcoplasmic reticular vesicles and single ryanodine receptors). Thymol induced a concentration-dependent negative inotropic action in both canine and guinea pig preparations (EC50=297+/-12 muM in dog). However, low concentrations of thymol reduced intracellular calcium transients in guinea pig hearts without decreasing contractility. At higher concentrations both calcium transients and contractions were suppressed. In canine sarcoplasmic reticular vesicles thymol induced rapid release of calcium (V-max=0.47+/-0.04 nmol s(-1), EC50=258+/-21 muM, Hill coefficient=3.0+/-0.54), and decreased the activity of the calcium pump (EC50=253+/-4.7 muM, Hill coefficient=1.62+/-0.05). Due to the less sharp concentration-dependence of the ATPase inhibition, this effect was significant from 50 muM, whereas the thymol-induced calcium release only from 100 muM. In single ryanodine receptors incorporated into artificial lipid bilayer thymol induced long lasting openings, having mean open times increased with 3 orders of magnitude, however, the specific conductance of the channel remained unaltered. This effect of thymol was not voltage-dependent and failed to prevent the binding of ryanodine. In conclusion, the negative inotropic action of thymol can be explained by reduction in calcium content of the sarcoplasmic reticulum due to the combination of the thymol-induced calcium release and inhibition of the calcium pump. The calcium-sensitizer effect, observed at lower thymol concentrations, indicates that thymol is likely to interact with the contractile machinery also. (C) 2003 Elsevier Inc. All rights reserved.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:Life Sciences. - 74 : 7 (2004), p. 909-921. -
További szerzők:Szigeti Gyula (1969-) (élettanász, elektrofiziológus) Szegedi Csaba Sárközi Sándor (1966-) (élettanász) Magyar János (1961-) (élettanász) Bányász Tamás (1960-) (élettanász) Csernoch László (1961-) (élettanász) Kovács László (1939-) (élettanász) Nánási Péter Pál (1956-) (élettanász) Jóna István (1948-) (élettanász, fizikus)
Internet cím:DOI
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