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001-es BibID:	BIBFORM052173
Első szerző:	Czikora Ágnes (molekuláris biológus)
Cím:	Structure-activity relationships of vanilloid receptor agonists for arteriolar TRPV1 / Á. Czikora, E. Lizanecz, P. Bakó, I. Rutkai, F. Ruzsnavszky, J. Magyar, R. Pórszász, T. Kark, A. Facskó, Z. Papp, I. Édes, A. Tóth
Dátum:	2012
ISSN:	0007-1188
Megjegyzések:	Summary Background and purpose: The vanilloid receptor 1 (TRPV1) plays a role in the activation of sensory neurons by various painful stimuli and became a therapeutic target. However, functional TRPV1 expression was also observed in the peripheral arteries affecting microvascular diameter. Experimental approach: Sensory TRPV1 activation was measured by eye wiping tests. Arteriolar TRPV1 mediated smooth muscle specific responses (arteriolar diameter, changes in intracellular Ca2+) were determined in isolated, pressurized skeletal muscle arterioles (from the rat and wild type or TRPV1-/- mice, n = 130) or in isolated canine smooth muscle cells. Vascular pharmacology of TRPV1 agonists (potency, efficacy, kinetics of action and receptor desensitization) was determined in isolated skeletal muscle arteries of the rat. Key results: Capsaicin evoked a similar constriction as norepinephrine, which was absent in TRPV knockout mice and was competitively inhibited by a TRPV1 antagonist AMG9810. Capsaicin activation resulted in an increase in intracellular Ca2+ in the arteriolar wall as well as in isolated smooth muscle cells. Other TRPV1 agonists evoked similar vascular constrictions (MSK-195, JYL-79) or were without effect (resiniferatoxin, JYL-273), although all resulted in a sensory activation (eye wiping). Maximal dose of agonists gave different kinetics of arteriolar response. A complete desensitization (tachyphylaxis) of arteriolar TRPV1 was observed (with the exception of capsaicin). Application of the partial agonist JYL-1511 suggested that about 10% TRPV1 activation is sufficient to evoke vascular tachyphylaxis without sensory activation. Conclusions and implications: Our data suggests that arteriolar TRPV1 has different structure-activity relationship compared to sensory neuron located receptor in the rat.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban vanilloid receptor (TRPV1) resistance artery vascular autoregulation
Megjelenés:	British Journal of Pharmacology. - 165 : 6 (2012), p. 1801-1812. -
További szerzők:	Lizanecz Erzsébet (1978-) (orvos) Bakó P. Rutkai Ibolya (1985-) (molekuláris biológus) Ruzsnavszky Ferenc (1984-) (élettanász) Magyar János (1961-) (élettanász) Pórszász Róbert (1965-) (farmakológus, klinikai farmakológus) Kark Tamás (1981-) (orvos) Facskó Andrea (1953-) (szemész) Papp Zoltán (1965-) (kardiológus, élettanász) Édes István (1952-) (kardiológus) Tóth Attila (1971-) (biológus)
Pályázati támogatás:	TÁMOP-4.2.1/B-09/1/KONV-2010-0007 TÁMOP Vascularis rizikó- és stroke betegek vizsgálata K68077 OTKA K84300 OTKA ETT 377/2009 Egyéb
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001-es BibID:	BIBFORM037346
Első szerző:	Szentandrássy Norbert (élettanász)
Cím:	Role of action potential configuration and the contribution of Ca2+ and K+ currents to isoprenaline-induced changes in canine ventricular cells / N. Szentandrássy, V. Farkas, L. Bárándi, B. Hegyi, F. Ruzsnavszky, B. Horváth, T. Bányász, J. Magyar, I. Márton, P. P. Nánási
Dátum:	2012
ISSN:	0007-1188
Megjegyzések:	BACKGROUND AND PURPOSE: Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca2+ current (ICa), slow delayed rectifier K+ current (IKs) and fast delayed rectifier K+ current (IKr)were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from varioustransmural locations.EXPERIMENTAL APPROACHAction potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques.KEY RESULTSIn myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the IKr blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the IKs blocker HMR-1556. Bothaction potential shortening and elevation of the plateau were prevented by pretreatment with the ICa blocker nisoldipine.Action potential voltage clamp experiments revealed a prominent slowly inactivating ICa followed by a rise in IKs, both currents increased with increasing the cycle length.CONCLUSIONS AND IMPLICATIONSThe effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of IKs ? but not IKr ? may be responsible for the observed shortening of action potentials
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban heart action potential calcium current potassium current
Megjelenés:	British Journal of Pharmacology. - 167 : 3 (2012), p. 599-611. -
További szerzők:	Farkas Viktória Bárándi László (1984-) (élettanász) Hegyi Bence (1987-) (élettanász) Ruzsnavszky Ferenc (1984-) (élettanász) Horváth Balázs (1981-) (élettanász) Bányász Tamás (1960-) (élettanász) Magyar János (1961-) (élettanász) Márton Ildikó (1954-) (fogszakorvos) Nánási Péter Pál (1956-) (élettanász)
Pályázati támogatás:	TÁMOP-4.2.1/B-09/1/KONV-2010-0007 TÁMOP A feszültségfüggő K-csatornák szerepe excitábilis sejtekben
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