Probenecid: novel use as a non-injurious positive inotrope acting via cardiac TRPV2 stimulation Journal Article

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Authors: Koch, S. E.; Gao, X; Haar, L; Jiang, M.; Lasko, V. M.; Robbins, N.; Cai, W.; Brokamp, C.; Varma, P.; Tranter, M.; Liu, Y; Ren, X; Lorenz, J. N.; Wang, H. S.; Jones, W. K.; Rubinstein, J.
Article Title: Probenecid: novel use as a non-injurious positive inotrope acting via cardiac TRPV2 stimulation
Abstract: 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 Ca(2+) 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 Ca(2+).
Journal Title: Journal of Molecular and Cellular Cardiology
Volume: 53
Issue: 1
ISSN: 1095-8584; 0022-2828
Publisher: Unknown  
Journal Place: England
Date Published: 2012
Start Page: 134
End Page: 144
Language: eng
DOI/URL:

10.1016/j.yjmcc.2012.04.011
Notes: LR: 20140408; CI: Copyright (c) 2012; GR: ES017263/ES/NIEHS NIH HHS/United States; GR: HL007382/HL/NHLBI NIH HHS/United States; GR: HL091478/HL/NHLBI NIH HHS/United States; GR: HL26057/HL/NHLBI NIH HHS/United States; GR: HL64018/HL/NHLBI NIH HHS/United States; GR: R01 ES017263/ES/NIEHS NIH HHS/United States; GR: R01 HL091478/HL/NHLBI NIH HHS/United States; GR: T1 UL1RR026314/RR/NCRR NIH HHS/United States; GR: UL1 TR000077/TR/NCATS NIH HHS/United States; JID: 0262322; 0 (Calcium Channels); 0 (Cardiotonic Agents); 0 (RNA, Messenger); 0 (TRPV Cation Channels); 0 (Trpv2 protein, mouse); PO572Z7917 (Probenecid); SY7Q814VUP (Calcium); NIHMS373871; OID: NLM: NIHMS373871; OID: NLM: PMC3372642; 2012/03/15 [received]; 2012/03/28 [revised]; 2012/04/16 [accepted]; 2012/04/27 [aheadofprint]; ppublish