The antiepileptic drug phenytoin affects sodium transport in toad epithelium.
The effects of phenytoin on isolated Pleurodema thaul toad skin were investigated. Low (micromolar) concentrations of the antiepileptic agent applied to the outside surface of the toad epithelium increased the electrical parameters (short-circuit current and potential difference) by over 40%, reflecting stimulation of Na(+) transport, whereas higher (millimolar concentrations, outside and inside surface) decreased both electric parameters, the effect being greater at the inside surface (40% and 80% decrease, respectively). The amiloride test showed that the stimulatory effect was accompanied by an increase and the inhibitory effect by a decrease in the sodium electromotive force (ENa). It is concluded that the drug interaction with membrane lipid bilayers might result in a distortion of the lipid-protein interface contributing to disturbance of Na(+) epithelial channel activity. After applying the Na(+)-K(+)-ATPase blocker ouabain and replacing the Na(+) ions in the outer Ringer's solution by choline, it was concluded that both active and passive transport are involved in sodium absorption, although active transport predominates.
Suwalsky
Mario
M
Faculty of Chemical Sciences, University of Concepción, Casilla 160-C, Concepcion, Chile. Electronic address: msuwalsk@udec.cl.
Mennickent
Sigrid
S
Faculty of Pharmacy, University of Concepción, Casilla 160-C, Concepcion, Chile.
Norris
Beryl
B
Faculty of Biological Sciences, University of Concepción, Casilla 237, Concepcion, Chile.
Cárdenas
Hernan
H
Faculty of Biological Sciences, University of Concepción, Casilla 237, Concepcion, Chile.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002025:Bufonidae / Q000502:physiology*; D002794:Choline / Q000494:pharmacology; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D010042:Ouabain; D010672:Phenytoin; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D002794:Choline