Probenecid: Novel use as a non-injurious positive inotrope acting via cardiac TRPV2 stimulation

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• 作者：Sheryl E. Kochp>ap>p> ; p>p>1p> ; Xiaoqian Gaop>bp>p> ; p>p>1p> ; Lauren Haarp>cp> ; Min Jiangp>ap> ; Valerie M. Laskop>cp> ; Nathan Robbinsp>ap> ; Wenfeng Caip>bp> ; Cole Brokampp>bp> ; Priyanka Varmap>ap> ; Michael Tranterp>bp> ; Yong Liup>bp> ; Xiaoping Renp>bp> ; John N. Lorenzp>cp> ; Hong-Sheng Wangp>bp> ; W. Keith Jonesp>bp> ; Jack Rubinsteinp>ap>p> ; p>p>rubinsjk@ucmail.uc.edup>
• 关键词：TRPV2 ; Probenecid ; Echocardiography ; Inotropic agent ; Calcium handling
• 刊名：Journal of Molecular and Cellular Cardiology
• 出版年：2012
• 期刊代码：171_00222828
• 类别：bio
• 出版时间：July, 2012
• 卷：53
• 期：1
• 页码：134-144
• 文件大小：1016 K

摘要

Probenecid is a highly lipid soluble benzoic acid derivative originally used to increase serum antibiotic concentrations. It was later discovered to have uricosuric effects and was FDA approved for gout therapy. It has recently been found to be a potent agonist of transient receptor potential vanilloid 2 (TRPV2). We have shown that this receptor is in the cardiomyocyte and report a positive inotropic effect of the drug. Using echocardiography, Langendorff and isolated myocytes, we measured the change in contractility and, using TRPV2p>鈭?鈭?/sup> mice, proved that the effect was mediated by TRPV2 channels in the cardiomyocytes. Analysis of the expression of Cap>2 +p> handling and 尾-adrenergic signaling pathway proteins showed that the contractility was not increased through activation of the 尾-ADR. We propose that the response to probenecid is due to activation of TRPV2 channels secondary to SR release of Cap>2 +p>.