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您的检索式：作者名="Alfonso Trezza"
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| 1 | Ritanserin blocks CaV1.2 channels in rat artery smooth muscles: electrophysiological, functional, and computational studies显示文摘CaV1.2 channel blockers or 5-HT2 receptor antagonists constitute effective therapy for Raynaud’s syndrome.A functional link between the inhibition of 5-HT2 receptors and CaV1.2 channel blockade in arterial smooth muscles has been hypothesized.Therefore,the effects of ritanserin,a nonselective 5-HT2 receptor antagonist,on vascular CaV1.2 channels were investigated through electrophysiological,functional,and computational studies.Ritanserin blocked CaV1.2 channel currents(ICa1.2)in a concentration-dependent manner(Kr=3.61µM);ICa1.2 inhibition was antagonized by Bay K 8644 and partially reverted upon washout.Conversely,the ritanserin analog ketanserin(100µM)inhibited ICa1.2 by^50%.Ritanserin concentration-dependently shifted the voltage dependence of the steady-state inactivation curve to more negative potentials(Ki=1.58µM)without affecting the slope of inactivation and the activation curve,and decreased ICa1.2 progressively during repetitive(1 Hz)step depolarizations(use-dependent block).The addition of ritanserin caused the contraction of single myocytes not yet dialyzed with the conventional method.Furthermore,in depolarized rings,ritanserin,and to a lesser extent,ketanserin,caused a concentration-dependent relaxation,which was antagonized by Bay K 8644.Ritanserin and ketanserin were docked at a region of the CaV1.2α1C subunit nearby that of Bay K 8644;however,only ritanserin and Bay K 8644 formed a hydrogen bond with key residue Tyr-1489.In conclusion,ritanserin caused in vitro vasodilation,accomplished through the blockade of CaV1.2 channels,which was achieved preferentially in the inactivated and/or resting state of the channel.This novel activity encourages the development of ritanserin derivatives for their potential use in the treatment of Raynaud’s syndrome. | Fabio Fusi Alfonso Trezza Giampietro Sgaragli Ottavia Spiga Simona Saponara Sergio Bova | 2020 | Acta Pharmacologica Sinica2020，41，9： | 0 |
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