Effects of N-n-butyl haloperidol iodide on the rat myocardial sarcoplasmic reticulum Ca(2+)-ATPase during ischemia/reperfusion.

Abstract

We have previously shown that N-n-butyl haloperidol iodide (F(2)), a newly synthesized compound, reduces ischemia/reperfusion (I/R) injury by preventing intracellular Ca(2+) overload through inhibiting L-type calcium channels and outward current of Na(+)/Ca(2+) exchanger. This study was to investigate the effects of F(2) on activity and protein expression of the rat myocardial sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) during I/R to discover other molecular mechanisms by which F(2) maintains intracellular Ca(2+) homeostasis. In an in vivo rat model of myocardial I/R achieved by occluding coronary artery for 30-60 min followed by 0-120 min reperfusion, treatment with F(2) (0.25, 0.5, 1, 2 and 4 mg/kg, respectively) dose-dependently inhibited the I/R-induced decrease in SERCA activity. However, neither different durations of I/R nor different doses of F(2) altered the expression levels of myocardial SERCA2a protein. These results indicate that F(2) exerts cardioprotective effects against I/R injury by inhibiting I/R-mediated decrease in SERCA activity by a mechanism independent of SERCA2a protein levels modulation.

• Authors: Yan-Mei Zhang, Chun-Yan Wang, Fu-Chun Zheng, Fen-Fei Gao, Yi-Cun Chen, Zhan-Qin Huang, Zheng-Yuan Xia, Michael G Irwin, Wei-Qiu Li, Xing-Ping Liu, Yan-Shan Zheng, Han Xu, Gang-Gang Shi
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 425 Issue 2 Pg. 426-30 (Aug 24 2012) ISSN: 1090-2104 [Electronic] United States
• PMID: 22846577 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Cardiotonic Agents
• N-n-butyl haloperidol iodide
• Sarcoplasmic Reticulum Calcium-Transporting ATPases
• Haloperidol

Topics

• Animals
• Cardiotonic Agents (pharmacology)
• Haloperidol (analogs & derivatives, pharmacology)
• In Vitro Techniques
• Male
• Microscopy, Electron, Transmission
• Myocardial Reperfusion Injury (enzymology, pathology)
• Myocardium (enzymology, ultrastructure)
• Rats
• Rats, Sprague-Dawley
• Sarcoplasmic Reticulum (drug effects, enzymology)
• Sarcoplasmic Reticulum Calcium-Transporting ATPases (antagonists & inhibitors, biosynthesis)