title: Structural and functional response of the isolated toad skin to mucosal lithium.
abstract: Structural and functional changes induced by long-term Li-exposure of the outer surface of toad skin was studied. Electron microscopy revealed that total Na by Li replacement in the outer compartment of short-circuited toad skin promotes a conspicuous cellular damage expressed as focal swollen cells with altered intercellular spaces and nuclear morphology. Short-circuit current (SCC) decreases by about 70% over the first 60 min after 115 mmol/l Li-exposure. An amiloride sensitive transepithelial Li transport remains intact over a further 150 min despite the epithelial damage, indicating that the pathways across the apical barrier are functioning. Increase of the paracellular permeability is detected by elevation of Na-efflux. Partial 50% or 10% Na by Li replacements induce minor structural alterations and are not sufficient to trigger appreciable Na-efflux and SCC alterations. Therefore, low Li concentrations are less effective than 115 mmol/l in promoting morphofunctional responses. Although ouabain and Li reduce the SCC, ouabain does not promote structural lesions, showing that Li-inhibition of Na transport by itself is not responsible for the observed morphological alterations. In the light of this study, Li utilization as a tool to investigate transepithelial Na transport requires careful judgement.
mesh_terms: D000818:Animals; D002024:Bufo marinus; D004848:Epithelium / Q000187:drug effects; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008854:Microscopy, Electron; D010042:Ouabain / Q000494:pharmacology; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
chemical_list: D010042:Ouabain; D008094:Lithium; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase