The protein tyrosine kinase pathway is not involved in the regulation of K+ transport across the rat colon.
The protein tyrosine kinase inhibitor, genistein, is known to activate the cystic fibrosis transmembrane regulator (CFTR) Cl- channel and to inhibit K+ currents across the rat colonic epithelium. The aim of the present study is to answer the question whether these effects are involved in the regulation of transepithelial K+ transport. Therefore, the action of genistein on K+ transport in rat proximal and distal colon was studied by measuring unidirectional fluxes, uptake and efflux of Rb+ in mucosa-submucosa preparations. All effects of genistein (5 x 10(-5) mol L(-1)) were tested in the presence of a low concentration of forskolin (2 x 10(-7) mol L(-1)), because prestimulation of the cAMP pathway has been shown to be a prerequisite for a secretory action of genistein. Forskolin caused an increase in the serosa-to-mucosa flux of Rb+ (J(Rb)sm) thereby stimulating net K+ secretion in the proximal and distal colon. None of these effects was further enhanced after administration of genistein. Neither mucosal uptake of Rb+, representing mainly the activity of the H+-K+-ATPase in the distal colon, nor serosal Rb+ uptake, representing, e.g. the activity of the Na+-K+-2Cl- cotransporter, were affected by genistein. Also the efflux of Rb+ across the apical or the basolateral membrane, an indicator for the apical and basolateral K+ conductance, was unchanged in the presence of genistein. These results demonstrate that the K+ channels inhibited by genistein are not involved in transepithelial K+ transport.
Heinke
B
B
Institut für Veterinär-Physiologie, Justus-Liebig-Universität Giessen, Germany.
Hörger
S
S
Diener
M
M
D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012414:Rubidium Radioisotopes
D004791:Enzyme Inhibitors; D015221:Potassium Channels; D012414:Rubidium Radioisotopes; D005576:Colforsin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D011188:Potassium; D007213:Indomethacin