Cytotoxic actions of palytoxin on aortic smooth muscle cells in culture.
Palytoxin (PTX), isolated from a zoanthid of the genus Palythoa, is the most potent marine toxin known. Intoxication by PTX leads to vasoconstriction, hemorrhage, ataxia, muscle weakness, ventricular fibrillation, pulmonary hypertension, ischemia and death. In this study, clonal A7r5 rat aortic smooth muscle cells were used to study the mechanism of PTX-mediated cytotoxicity. A7r5 cells exposed to PTX for > or = 15 min exhibited surface granularities, vacuoles and rounding. These alterations culminated in a loss of viability as indicated by marked increases in the release of lactate dehydrogenase. Electrophysiological recording from A7r5 cells disclosed a profound membrane depolarization and an increase in conductance to Na+ and K+. PTX-mediated cytotoxicity could not be reversed by washout or by the addition of 10 microM verapamil but was antagonized by 100 microM ouabain or by removal of extracellular Na+ or Ca2+. In light of the involvement of vascular smooth muscle in PTX poisoning, A7r5 cells could serve as a useful model to test specific drugs for treatment of PTX intoxication.
Sheridan
Robert E
RE
Neurotoxicology Branch, Pharmacology Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010, USA.
Deshpande
Sharad S
SS
Adler
Michael
M
D000178:Acrylamides / Q000633:toxicity*; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002460:Cell Line; D016764:Cell Polarity / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002999:Clone Cells; D003064:Cnidarian Venoms; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D051381:Rats; D014700:Verapamil / Q000494:pharmacology; D000095702:Polyether Toxins
D000178:Acrylamides; D002118:Calcium; D002121:Calcium Channel Blockers; D003064:Cnidarian Venoms; D007770:L-Lactate Dehydrogenase; D014700:Verapamil; C010272:palytoxin; D000095702:Polyether Toxins