The effect of EGF on electrolyte transport is mediated by tyrosine kinasesin the rabbit cortical collecting duct

Citation
S. Ookawara et al., The effect of EGF on electrolyte transport is mediated by tyrosine kinasesin the rabbit cortical collecting duct, MIN ELECT M, 25(3), 1999, pp. 191-198
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
MINERAL AND ELECTROLYTE METABOLISM
ISSN journal
0378-0392 → ACNP
Volume
25
Issue
3
Year of publication
1999
Pages
191 - 198
Database
ISI
SICI code
0378-0392(199905/06)25:3<191:TEOEOE>2.0.ZU;2-S
Abstract
Epidermal growth factor (EGF) inhibits amiloride-sensitive Na+ conductance in the apical membrane of the isolated rabbit cortical collecting duct. How ever, there is no information on the relationship between electrolyte trans port and tyrosine kinase. We examined the effect of EGF on transport of pot assium and chloride as well as sodium a nd the roles of tyrosine kinases in the rabbit cortical collecting duct using in vitro isolated tubular microp erfusion. Basolateral EGF depolarized the transepithelial voltage in a dose -dependent manner within a concentration range of 10(-10) in 10(-8) M. Baso lateral ouabain and luminal amiloride completely abolished EGF-induced depo larization. However, luminal BaCl2 did not abolish its depolarization. To c onfirm the mechanism, sodium, potassium, and chloride fluxes were measured in the presence of 10(-10) M EGF. EGF significantly decreased the lumen-to- bath isotope flux of sodium and chloride from 93.6+/-12.5 to 61.1+/-9.6 pmo l/mm/min (n=5, p < 0.05) and from 86.6 +/- 10.0 to 54.8 +/-9.7 pmol/mm/min (n=10, p<0.01), respectively. EGF also decreased net potassium secretion fr om -27.7+/-5.9 to -7.8+/-1.5 pmol/mm/min (n=6, p<0.01). To era mine whether EGF-induced depolarization is mediated by tyrosine kinase, tyrosine kinase inhibitors were applied from the basolateral side. Pretreatment with 1 mu g/ml herbimycin A for 120 min completely abolished EGF-induced depolarizati on (90.9+/-5.4%, n=4; NS). Herbimycin A itself also did not change the lume n-to-bath isotope flux of sodium and completely abolished the inhibition of Na+ absorption on EGF action (control 65.4+/-6.8, herbimycin A 61.8+/-6.3, EGF with herbimycin A 60.0+/-4.4 pmol/min/min, n=5; NS). In conclusion, EG F depolarizes transepithelial voltage by inhibiting sodium transport primar ily and potassium and chloride transport secondarily. These effects were bl ocked by nonspecific tyrosine kinase inhibitors.