6 results on '"Saponara, Simona"'
Search Results
2. The Novel Potent Multidrug Resistance Inhibitors N,N-bis(cyclohexanol)amine Aryl Esters Are Devoid of Vascular Effects.
- Author
-
Saponara, Simona, Gorelli, Beatrice, Tzankova, Virginia, Martelli, Cecilia, Teodori, Elisabetta, Sgaragli, Giampietro, and Fusi, Fabio
- Subjects
- *
MULTIDRUG resistance , *AMINES , *ARYLATION , *ESTERS , *BLOOD vessels , *AORTA , *MUSCLE cells , *LABORATORY rats - Abstract
The aim of this study was to investigate the effects of the four isomers (3a, 3b, 3c and 3d) of a novel multidrug resistance-reverting agent - 3,4,5-trimethoxybenzoic acid 4-(methyl-{4-[3-(3,4,5-trimethoxyphenyl)acryloyloxy]cyclohexyl}amino)cyclohexyl ester - on vascular functions in vitro. A comparison of their mechanical and electrophysiological actions in rat aorta rings and single rat tail artery myocytes, respectively, was performed. In rat aorta rings, 3a-d antagonized both 60 mmol/l K+- and phenylephrine-induced contraction in a concentration-dependent manner, with maximal relaxation values averaging 50% of controls, 3d being the most effective of the series. The vasorelaxing effect was similar either in presence or absence of intact endothelium. In rat tail artery myocytes, out of the four isomers, only 3a consistently inhibited Ba2+ current through Cav1.2 channels. Our results provide functional evidence that 3a-d are weak vasorelaxing agents, although at concentrations much higher than those effective for multidrug resistance reversion in cancer cells. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
3. Quercetin antagonism of Bay K 8644 effects on rat tail artery L-type Ca2+ channels
- Author
-
Saponara, Simona, Sgaragli, Giampietro, and Fusi, Fabio
- Subjects
- *
QUERCETIN , *MUSCLE cells , *CALCIUM channels , *DRUG antagonism , *VASCULAR smooth muscle , *LABORATORY rats - Abstract
Abstract: The functional interaction between two L-type Ca2+ channel activators, quercetin and (S)-(−)-methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)pyridine-5-carboxylate (Bay K 8644), has been investigated in vascular smooth muscle cells. L-type Ca2+ currents [I Ca(L)] were recorded in freshly isolated rat tail main artery myocytes using the whole-cell patch-clamp method. Bay K 8644 increased I Ca(L) in a concentration-dependent manner with a pEC50 value of 8.25. Pre-incubation of myocytes with concentrations of quercetin per se ineffective as an L-type Ca2+ channel activator (0.1 and 0.3 μM) inhibited significantly the maximal response evoked by Bay K 8644, but left unaltered its potency. Quercetin (0.1 μM) prevented the hyperpolarizing shift of the steady-state inactivation curve induced by 0.1 μM Bay K 8644 and its stimulation of I Ca(L) tail current intensity without modifying Bay K 8644-induced effects on I Ca(L) activation, inactivation, deactivation kinetics as well as on use-dependence and recovery from inactivation. Quercetin at nutritionally meaningful concentrations, limited the responsiveness of vascular L-type Ca2+ channels to the pharmacological stimulation operated by Bay K 8644. These data contribute to a better understanding of quercetin effects on experimental in vivo cardioprotection. [Copyright &y& Elsevier]
- Published
- 2008
- Full Text
- View/download PDF
4. Quercetin as a novel activator of L-type Ca[sup2+] channels in rat tail artery smooth muscle cells.
- Author
-
Saponara, Simona, Sgaragli, Giampietro, and Fusi, Fabio
- Subjects
- *
CALCIUM channels , *QUERCETIN , *MUSCLE cells , *PATCH-clamp techniques (Electrophysiology) , *LABORATORY rats - Abstract
1 The aim of this study was to investigate the effects of quereetin, a natural polyphenolic flavonoid, on voltage-dependent Ca[sup2+] channels of smooth muscle cells freshly isolated from the rat tail artery, using either the conventional or the amphotericin B-perforated whole-cell patch-clamp method. 2 Quercetin increased L-type Ca[sup2] current[I[sub Ca(L)] in a concentration- (pEC[sub50]= 5.09±0.05) and voltage-dependent manner and shifted the maximum of the current-voltage relationship by 10 mV in the hyperpolarizing direction, without, however, modifying the threshold and the equilibrium potential for Ca[sup2+], Quercetin-indueed I[subCa(L)] stimulation was reversible upon wash-out. T-type Ca[sup2] current was not affected by quercetin. 3 Quercetin shifted the voltage dependence of the steady-state inactivation and activation curves to more negative potentials by about 5.5 and 7.5 mV respectively, in the mid-potential of the curves as well as increasing the slope of activation. Quercetin slowed both the activation and the deactivation kinetics of the I[subCa(L)]. The inactivation time course was also slowed but only at voltages higher than 10 mV. Moreover quercetin slowed the rate of recovery from inactivation. 4 These results prove quercetin to be a naturally-occurring L-type Ca[sup2] channel activator. [ABSTRACT FROM AUTHOR]
- Published
- 2002
- Full Text
- View/download PDF
5. Negative chronotropism, positive inotropism and lusitropism of 3,5-di-t-butyl-4-hydroxyanisole (DTBHA) on rat heart preparations occur through reduction of RyR2 Ca2+ leak.
- Author
-
Pessina, Federica, Gamberucci, Alessandra, Chen, Jialin, Liu, Boyin, Vangheluwe, Peter, Gorelli, Beatrice, Lorenzini, Stefania, Spiga, Ottavia, Trezza, Alfonso, Sgaragli, Giampietro, and Saponara, Simona
- Subjects
- *
BUTYLATED hydroxyanisole , *SARCOPLASMIC reticulum , *ANTIOXIDANT analysis , *LABORATORY rats , *FLUORESCENCE yield , *PHYSIOLOGY - Abstract
Graphical abstract Abstract 3,5-Di- t -butyl-4-hydroxyanisole (DTBHA) is considered as an activator of the skeletal muscle sarcoplasmic reticulum (SR) Ca2+-uptake, endowed with antioxidant and L-type Ca2+ channel blocking activities. In this study we assessed the cardiac effects of DTBHA on Langendorff perfused rat hearts, isolated rat atria and rat cardiac SR membrane vesicles, as well as on several SERCA isoforms of membrane preparations. Moreover, in order to clarify its molecular mechanism of action Ca2+ imaging experiments were carried out on HEK293 cells transiently transfected with RyR2 channel. Docking of DTBHA at the rat RyR2 protein was investigated in silico. In Langendorff perfused rat hearts, DTBHA significantly increased, in a concentration-dependent manner, left ventricular pressure and diastole duration, while reducing heart rate and the time-constant of isovolumic relaxation, leaving unaltered coronary perfusion pressure. At the maximum concentration tested (30 µM), it significantly prolonged PQ interval, but left the corrected QT intervals unaffected. In spontaneously beating atria, DTBHA decreased sinus rate in a concentration-dependent manner. DTBHA, at concentrations higher than 10 µM, increased Ca2+ uptake in cardiac SR without affecting Ca2+-dependent ATPase activity assayed on several SERCA isoforms. Moreover, DTBHA antagonized thapsigargin-stimulated Ca2+ leak in cardiac SR and reduced caffeine-induced, RyR2-activated Ca2+ release in RyR2 expressing HEK293 cells. Using computational approaches, DTBHA showed a good affinity outline into binding sites of RyR2 protein. In conclusion, DTBHA behaved like a negative chronotropic, a positive inotropic and a lusitropic agent on rat heart preparations and improved cardiac SR Ca2+ uptake by lowering SR Ca2+ leak. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
6. The vasodilator papaverine stimulates L-type Ca2+ current in rat tail artery myocytes via a PKA-dependent mechanism.
- Author
-
Fusi, Fabio, Manetti, Fabrizio, Durante, Miriam, Sgaragli, Giampietro, and Saponara, Simona
- Subjects
- *
VASODILATORS , *CALCIUM ions , *LABORATORY rats , *MUSCLE cells , *CYCLIC-AMP-dependent protein kinase , *PHOSPHODIESTERASE inhibitors - Abstract
Papaverine is an opium alkaloid, primarily used as an antispasmodic drug and as a cerebral and coronary vasodilator. Its phosphodiesterase inhibitory activity promotes increase of cAMP levels mainly in the cytosol. As cAMP is known to modulate L-type Ca 2+ channel activity, here we tested the proposition that papaverine could affect vascular channel function. An in-depth analysis of the effect of papaverine on Ba 2+ or Ca 2+ current through L-type Ca 2+ channel [I Ba(L) or I Ca(L) ], performed in rat tail artery myocytes using either the whole-cell or the perforated patch-clamp method, was accompanied by a functional study on rat aorta rings. Papaverine increased current amplitude under both the perforated or whole-cell configuration. Stimulation of the current by papaverine was concentration-, V h -, frequency-, and charge carrier-dependent, and fully reverted by drug washout. The PKA inhibitor H89, but not the PKG inhibitor Rp-8-Br-cGMPS, antagonised papaverine- as well as IBMX- (another phosphodiesterase inhibitor) induced I Ba(L) stimulation. In cells pre-treated with IBMX, application of papaverine failed to increase current amplitude. Papaverine sped up the inactivation kinetics of I Ba(L) , though only at concentrations ≥ 30 μM, and shifted the voltage dependence of the inactivation curve to more negative potentials. In rings, the vasorelaxing activity of papaverine was enhanced by previous treatment with nifedipine. In conclusion, papaverine stimulates vascular L-type Ca 2+ channel via a PKA-dependent mechanism, thus antagonising its main vasodilating activity. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.