The effect of epinephrine on transport of K+, Na+, Cl−, and[Formula: see text] across the rat colon was studied using the Ussing chamber technique. Epinephrine (5 × 10−6 mol/l) induced a biphasic change in short-circuit current ( I sc) in distal and proximal colon: a transient increase followed by a long-lasting decay. The first phase of the I sc response was abolished in Cl−-poor solution or after bumetanide administration, indicating a transient induction of Cl− secretion. The second phase of the response to epinephrine was suppressed by apical administration of the K+channel blocker, quinine, and was concomitant with an increase in serosal-to-mucosal Rb+ flux, indicating that epinephrine induced K+ secretion, although this response was much smaller than the change in I sc. In addition, the distal colon displayed a decrease in mucosal-to-serosal and serosal-to-mucosal Cl−fluxes when treated with epinephrine. In the distal colon, indomethacin abolished the first phase of the epinephrine effect, whereas the second phase was suppressed by TTX. In the proximal colon, indomethacin and TTX were ineffective. The neuronally mediated response to epinephrine in the distal colon was suppressed by the nonselective β-receptor blocker, propranolol, and by the β2-selective blocker, ICI-118551, whereas the epithelial response in the proximal colon was suppressed by the nonselective α-blocker, phentolamine, and by the selective α2-blocker, yohimbine. These results indicate a segment-specific action of epinephrine on ion transport: a direct stimulatory action on epithelial α2-receptors in the proximal colon and an indirect action on secretomotoneurons via β2-receptors in the distal colon.

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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.