Protamine and other polycationic drugs inhibit calcium leak in cardiac cells during metabolic inhibition and free radical exposure.
We studied the effect of the polycationic compounds protamine, polybrene and gentamicin on the calcium leak induced by metabolic inhibition and free radical exposure in cultured neonatal rat cardiac cells. All of the drugs tested inhibited the calcium leak. The potency of the compound in this respect was related to the magnitude of the positive charge borne by the molecule. Protamine was the most potent drug tested. None of the drugs tested had more than a small effect on lactate dehydrogenase release. The physicochemical properties of these compounds lead us to predict that they are acting at negatively charged sites on the outer surface of the sarcolemma. We conclude that polycationic compounds, exemplified by protamine, are able to inhibit calcium overload. It is anticipated that this group of compounds may be effective as cardioprotective agents.
Clague
J R
JR
Cardiovascular Research Laboratories, UCLA School of Medicine.
Harvey
R
R
Langer
G A
GA
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D005609:Free Radicals; D005839:Gentamicins / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology; D006583:Hexadimethrine Bromide / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D011479:Protamines / Q000494:pharmacology*; D051381:Rats
D005609:Free Radicals; D005839:Gentamicins; D011479:Protamines; D006583:Hexadimethrine Bromide; D006493:Heparin; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D002118:Calcium