A new approach to the development of anti-ischemic drugs. Substances that counteract the deleterious effect of lysophosphatidylcholine on the heart.
Lysophosphatidylcholine (LPC) is an amphiphilic metabolite that can be produced from membrane-phospholipids by activation of phospholipase A2 (PLA2), and it accumulates in the heart during ischemia and reperfusion. It is known that LPC is an arrhythmogenic substance. Recent studies have revealed that LPC produces mechanical and metabolic derangements in perfused working rat hearts, and Ca(2+)-overload in isolated cardiac myocytes. Thus, LPC possesses an ischemia-like effect on the heart. LPC accumulated in the myocardium activates phospholipase A2, establishing a vicious circle; i.e. LPC itself has an ability to produce another LPC. Therefore, a drug that has an anti-LPC effect would protect or improve ischemia/reperfusion damage. This article will review the effect of LPC in relation to ischemia, and consider a possibility of developing new anti-ischemic drugs on the basis of the anti-LPC action.
Hashizume
H
H
Department of Pharmacology, Asahikawa Medical College, Japan.
Hoque
A N
AN
Magishi
K
K
Hara
A
A
Abiko
Y
Y
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002415:Cats; D004109:Dilazep / Q000031:analogs & derivatives / Q000494:pharmacology; D004789:Enzyme Activation; D006321:Heart / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008244:Lysophosphatidylcholines / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D013552:Swine; D013779:Tetrodotoxin / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; C092019:K 7259; D008244:Lysophosphatidylcholines; D013779:Tetrodotoxin; D011433:Propranolol; D010741:Phospholipases A; D054467:Phospholipases A2; D004109:Dilazep; D002118:Calcium