Pharmacological profile of KR-33028, a highly selective inhibitor of Na+/H+ exchanger

European Journal of Pharmacology
Yi-Sook JungByung Ho Lee

Abstract

We evaluated the cardioprotective effects of 4-cyano (benzo[b]thiophene-2-carbonyl)guanidine (KR-33028), a recently developed inhibitor of the Na+/H+ exchanger (NHE), on hypoxia-induced H9c2 cell death and on perfused rat hearts subjected to ischemia/reperfusion. KR-33028 inhibited in a concentration-dependent manner the recovery from acidosis induced by an NH4Cl prepulse in PS120 fibroblast cells expressing the human NHE-1 isoform (IC50: 2.59 microM). Treatment with KR-33028 (1-10 microM) significantly decreased hypoxia-induced necrotic cell death and apoptotic cell death in H9c2 cells. KR-33028 significantly inhibited hypoxia-induced increases in cytosolic and mitochondrial Ca2+ level and cytochrome c release, and recovered hypoxia-induced Delta psi(m) reduction. In the perfused rat hearts subjected to 30 min of ischemia and 30 min of reperfusion, KR-33028 (1-10 microM) improved cardiac contractility, decreased lactate dehydrogenase release, and increased content of tissue ATP, creatine phosphate and glycogen in a concentration-dependent manner. In addition, KR-33028 did not produce significant acute or subacute toxicity in the rats at doses tested. Our results suggest that a novel NHE-1 inhibitor KR-33028 possesses potent ca...Continue Reading

References

Feb 24, 1997·The Journal of Cell Biology·D F BabcockB Hille
Apr 14, 1999·Cell Death and Differentiation·G Kroemer
May 5, 1999·The Journal of Physiology·C H LeemR D Vaughan-Jones
Mar 1, 2002·Journal of the American College of Cardiology·Metin Avkiran, Michael S Marber
Feb 4, 2003·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·S S SmailiR J Youle
Jul 3, 2003·Nature Reviews. Molecular Cell Biology·Sten OrreniusPierluigi Nicotera
Feb 21, 2004·European Journal of Pharmacology·He-Ying SunZhi-Qing Zhao

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Citations

Dec 17, 2009·Antioxidants & Redox Signaling·Amadou K S CamaraDavid F Stowe
Apr 14, 2012·Cardiovascular Research·David Garcia-DoradoHans Michael Piper
May 8, 2007·European Journal of Pharmacology·Juno KimKyung Hwan Kim
Dec 10, 2008·Expert Opinion on Therapeutic Targets·Larry Fliegel
Sep 11, 2007·Biopharmaceutics & Drug Disposition·Young Hoon KimHye Suk Lee
Nov 5, 2008·Biological & Pharmaceutical Bulletin·Kwang-Seok OhByung Ho Lee
Sep 12, 2019·Physiological Reviews·S F Pedersen, L Counillon

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