Cardiotoxicity of Naja nigricollis phospholipase A2 is not due to alterations in prostaglandin synthesis.
The basic phospholipase A2 from Naja nigricollis snake venom is cardiotoxic, causing decreased contractility and arrhythmias at concentrations which induce low levels of phospholipid hydrolysis. Cardiac tissue has a high content of arachidonic acid at the sn-2 position of the major membrane phospholipids, thus increased prostaglandin synthesis might contribute to the cardiotoxic effects of N. nigricollis phospholipase A2. Intracellular action potentials and cardiac contractility were monitored in the isolated right ventricular wall of the rat heart exposed for 1 hr to N. nigricollis phospholipase A2, with or without indomethacin, or to arachidonic acid. The tissues were homogenized, prostaglandins extracted and the 6-keto PGF1 alpha and PGE2 content of the hearts determined. The physiologic effects and prostaglandin content of hearts treated with N. nigricollis phospholipase A2 were not altered by indomethacin nor mimicked by concentrations of arachidonic acid comparable to that present in N. nigricollis phospholipase A2-treated tissue. These results support our previous suggestion that exogenously applied N. nigricollis phospholipase A2 causes cardiotoxic effects by a mechanism that is independent of phospholipid hydrolysis.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D004546:Elapid Venoms / Q000032:analysis; D006331:Heart Diseases / Q000139:chemically induced / Q000378:metabolism*; D006868:Hydrolysis; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010740:Phospholipases / Q000494:pharmacology*; D010741:Phospholipases A / Q000302:isolation & purification / Q000494:pharmacology*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D004546:Elapid Venoms; D010743:Phospholipids; D011453:Prostaglandins; D016718:Arachidonic Acid; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D007213:Indomethacin