Effects of apical vs. basolateral palytoxin on LLC-PK1 renal epithelia.
Research on palytoxin focuses on its action as a tumor promoter and its ionophoretic action in cell membranes. The first property is unusual because palytoxin is not a protein kinase C activator. The second property is remarkable in that it may require interaction with the Na(+)-K(+)-adenosinetriphosphatase (ATPase). Our studies here with palytoxin exposure to the LLC-PK1 renal epithelial cells have yielded the following results: 1) unlike protein kinase C-activating tumor promoters (tetradecanoylphorbol 12,13-acetate or teleocidin), palytoxin does not produce a specific effect on the tight junctions between epithelia; 2) palytoxin instead produces an irreversible cytotoxic effect characterized by a pronounced cell swelling associated with sharply elevated levels of intracellular Na+ and decreased levels of intracellular K+; 3) these fluctuations in intracellular Na+ and K+ levels are explained by marked elevations in the membrane flux of 22Na+ and 86Rb+; 4) the electrophysiological reflection of these altered ion fluxes is a pronounced depolarization of the cell sheet if palytoxin is presented to the basolateral cell surface and a pronounced hyperpolarization (due to sharply elevated apical Na+ flux and transepithelial short-circuit current) if palytoxin is administered apically; 5) the apical effect of palytoxin can be blocked by apical ouabain; and 6) this apical effect of palytoxin decreases as a function of the age of the cell sheet. This first report of palytoxin action in a polar epithelial cell system provides additional evidence for palytoxin effects being mediated by contact with the Na(+)-K(+)-ATPase. It also adds to a growing literature suggesting the existence of Na(+)-K(+)-ATPase in the apical cell surface of epithelia under certain conditions.
Lankenau Medical Research Center, Wynnewood, Pennsylvania 19096.
J M
JM
Mullin
K V
KV
Snock
M T
MT
McGinn
D000178:Acrylamides; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D003064:Cnidarian Venoms / Q000494:pharmacology*; D004553:Electric Conductivity / Q000187:drug effects; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D007668:Kidney; D007700:Kinetics; D008235:Lyngbya Toxins / Q000494:pharmacology; D008353:Mannitol / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D012413:Rubidium / Q000378:metabolism; D000095702:Polyether Toxins
D000178:Acrylamides; D003064:Cnidarian Venoms; D008235:Lyngbya Toxins; D008353:Mannitol; D012413:Rubidium; C022176:teleocidins; C010272:palytoxin; D000095702:Polyether Toxins