IngentaConnect The protein tyrosine kinase pathway is not involved in the regula...

Abstract:

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 × 10⁻⁵ mol L⁻¹) were tested in the presence of a low concentration of forskolin (2 × 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.

Keywords: electrolyte transport; genistein; H+-K+-ATPase; K+ channels; K+ transport; Na+-K+-2 Cl− cotransporter; rat colon

Document Type: Research article

DOI: 10.1046/j.1365-201x.1999.00523.x

Affiliations: 1: Institut für Veterinär-Physiologie, Justus-Liebig-Universität Gießen, Germany

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The protein tyrosine kinase pathway is not involved in the regulation of K+ transport across the rat colon

The protein tyrosine kinase pathway is not involved in the regulation of K⁺ transport across the rat colon