RESUMO
Using the voltage-clamp technique, a possible role of microtubules and vesicular transport in the effect of pharmacological analogue of oxidized glutathione, drug glutoxim, on Na+ transport in the frog Rana temporaria skin was investigated. It was shown for the first time that the disrupter of microtubules nocodazole or inhibitor of vesicular transport brefeldin A similarly modulate (completely inhibit) the stimulatory effect of glutoxim on Na+ transport. The data suggest the involvement of reorganization of microtubules and vesicular transport in the regulatory effect of glutoxim on Na+ transport. .
Assuntos
Brefeldina A/farmacologia , Nocodazol/farmacologia , Oligopeptídeos/farmacologia , Inibidores da Síntese de Proteínas/farmacologia , Pele/metabolismo , Sódio/metabolismo , Moduladores de Tubulina/farmacologia , Animais , Transporte de Íons/efeitos dos fármacos , Rana temporariaRESUMO
Using voltage-clamp technique, the possible role of the cytoskeleton in the effect of pharmacological analogue of oxidized glutathione (GSSG), drug glutoxim, on Na+ transport in the frog Rana temporaria skin was investigated. It was shown for the first time that preincibation of the skin with the microtubular disrupter, nocodazole, actin filament disrupter, cytochalasin D or protein phosphatase PP1/PP2A inhibitor, calyculin A, significantly decrease the stimulatory effect of glutoxim on Na+ transport. The data suggest the involvement of microtubules and microfilaments in the regulatory effect of glutoxim on Na+ transport in frog skin and that reorganization of actin filaments or microtubules leads to inhibition of stimulatory effect of glutoxim on Na+ transport in frog skin epithelia.
Assuntos
Citoesqueleto de Actina/fisiologia , Microtúbulos/fisiologia , Oligopeptídeos/farmacologia , Pele/efeitos dos fármacos , Sódio/metabolismo , Citoesqueleto de Actina/efeitos dos fármacos , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Citocalasina D/farmacologia , Dissulfetos/farmacologia , Transporte de Íons/efeitos dos fármacos , Transporte de Íons/fisiologia , Masculino , Toxinas Marinhas , Microtúbulos/efeitos dos fármacos , Nocodazol/farmacologia , Oxazóis/farmacologia , Técnicas de Patch-Clamp , Rana temporaria , Tiazolidinas/farmacologiaRESUMO
Using voltage-clamp technique, the role of tyrosine kinases and phosphatidylinositol kinases in the effect of oxidized glutathione (GSSG) and its pharmacological analogue, drug glutoxim, on Na+ transport in the frog Rana temporaria skin was investigated. It was shown for the first time that preincubation of the skin with tyrosine kinase inhibitor genistein or with two structurally distinct phosphatidylinositol kinase inhibitors, wortmannin and LY294002, significantly decreased the stimulatory effect of GSSG or glutoxim on Na+ transport. The data suggest that GSSG and glutoxim might transactivate insulin receptor in the basolateral membrane of epithelial cells and trigger the signaling cascade, involving tyrosine kinases and phosphatidylinositol kinases, which lead to Na+ transport stimulation in frog skin.
Assuntos
Dissulfeto de Glutationa/farmacologia , Oligopeptídeos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Proteínas Tirosina Quinases/metabolismo , Sódio/metabolismo , Androstadienos/farmacologia , Animais , Cromonas/farmacologia , Genisteína/farmacologia , Transporte de Íons/efeitos dos fármacos , Masculino , Antígenos de Histocompatibilidade Menor , Morfolinas/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Rana temporaria , Pele/efeitos dos fármacos , Pele/metabolismo , WortmaninaRESUMO
The review summarizes recent data on the structural and functional organization and regulation mechanisms of Na+ transport in epithelial systems. The review is focused on the structure, function, regulation and pathology of epithelial Na+ channels, which are critical for Na+ homeostasis maintenance and blood pressure control.
