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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
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
Vascularis rizikó- és stroke betegek vizsgálata
ETT 377/2009
Internet cím:Szerző által megadott URL
Intézményi repozitóriumban (DEA) tárolt változat


001-es BibID:BIBFORM003870
Első szerző:Kark Tamás (orvos)
Cím:Tissue-specific regulation of microvascular diameter : opposite functional roles of neuronal and smooth muscle located vanilloid receptor-1 / Tamás Kark, Zsolt Bagi, Erzsébet Lizanecz, Enikő T. Pásztor, Nóra Erdei, Ágnes Czikora, Zoltán Papp, István Édes, Róbert Pórszász, Attila Tóth
Megjegyzések:The transient receptor potential type V1 channel (vanilloid receptor 1, TRPV1) is a Ca2+ -permeable nonspecific cation channel activated by various painful stimuli including ischemia. We hypothesized that TRPV1 is expressed in the arterioles and is involved in the regulation of microvascular tone. We found that TRPV1 stimulation by capsaicin (intra-arterial administration) of the isolated, perfused right hind limb of the rat increased vascular resistance (by 98 ± 21 mm Hg at 10 gamma g) in association with decreased skeletal muscle perfusion and elevation of skin perfusion (detected by dual-channel laser Doppler flowmetry). Denervation of the hind limb did not affect capsaicin-evoked changes in vascular resistance and tissue perfusion in the hind limb but reduced the elevation of perfusion in the skin. In isolated, pressurized skeletal (musculus gracilis) muscle arterioles (diameter, 147 ± 35 gamma m), capsaicin had biphasic effects: at lowe concentrations, capsaicin (up to 10 nM) evoked dilations (maximum, 32 ± 13%), whereas higher concentrations (0.1-1 gamma M) elicited substantial constrictions (maximum, 66 ± 7%). Endothelium removal or inhibition of nitric-oxide synthase abolished capsaicin-induced dilations but did not affect arteriolar constriction. Expression of TRPV1 was detected by reverse transcriptase-polymerase chain reaction in the aorta and in cultured rat aortic vascular smooth muscle cells (A7r5). Immunohistochemistry revealed expression primarily in the smooth muscle layers of the gracilis arteriole. These data demonstrate the functional expression of TRPV1 in vascular smooth muscle cells mediating vasoconstriction of the resistance arteries. Because of the dual effects of TRPV1 stimulation on the arteriolar diameter (dilation in skin, constriction in skeletal muscle), we propose that TRPV1 ligands represent drug candidates for tissue-specific modulation of blood distribution.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
calcitonin gene-related peptide
Megjelenés:Molecular Pharmacology. - 73 : 5 (2008), p. 1405-1412. -
További szerzők:Bagi Zsolt (1974-) (orvos) Lizanecz Erzsébet (1978-) (orvos) Pásztorné Tóth Enikő (1966-) (laboratóriumi analitikus) Erdei Nóra (1979-) (orvos) Czikora Ágnes (1982-) (molekuláris biológus) Papp Zoltán (1965-) (kardiológus, élettanász) Édes István (1952-) (kardiológus) Pórszász Róbert (1965-) (farmakológus, klinikai farmakológus) Tóth Attila (1971-) (biológus)
Internet cím:elektronikus változat
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