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

作者：Koch, Sheryl E.; Gao, Xiaoqian; Haar, Lauren; Jiang, Min; Lasko, Valerie M.; Robbins, Nathan; Cai, Wenfeng; Brokamp, Cole; Varma, Priyanka; Tranter, Michael; Liu, Yong; Ren, Xiaoping; Lorenz, John N.; Wang, Hong-Sheng; Jones, W. Keith; Rubinstein, Jack^*

来源：Journal of Molecular and Cellular Cardiology, 2012, 53(1): 134-144.

DOI：10.1016/j.yjmcc.2012.04.011

• TRPV2
• Probenecid
• Echocardiography
• Inotropic agent
• Calcium handling

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 TRPV2(-/-) mice, proved that the effect was mediated by TRPV2 channels in the cardiomyocytes. Analysis of the expression of Ca2+ handling and beta-adrenergic signaling pathway proteins showed that the contractility was not increased through activation of the beta-ADR. We propose that the response to probenecid is due to activation of TRPV2 channels secondary to SR release of Ca2+.

• 出版日期2012-7