Adrenoceptor-mediated secretion across the rat colonic epithelium

Norepinephrine evoked a biphasic change in short-circuit current (Isc) across the proximal and distal colon of the rat. The (1) phase of the current response consisted of a transient increase, which was followed by a long-lasting decrease during the (2) phase. The (1) phase, which is assumed to represent Cl(-) secretion, was resistant against classical adrenoceptor antagonists, but was inhibited by the beta(3)-adrenoceptor antagonist 3-(2-ethylpenoxy)-1-[(1S-1,2,3, 4-tetrahydronaphth-1-ylaminol-(2S)-propranol oxalate (SR 59230A) in the proximal colon and by the non-selective beta-adrenoceptor antagonist bupranolol in both colonic segments. Vice versa, the increase in Isc was mimicked by the beta(3)-adrenoceptor agonist, (R*, R*)-(+/-)-4-[2-[(2-(3-chlorophenyl)-2-hydroxyethyl)amino]propyl]pheno xyacetic acid (BRL 37344). The (2) phase of the norepinephrine-induced Isc, which is assumed to represent K(+) secretion, was inhibited by yohimbine in the proximal colon, suggesting the mediation by alpha(2)-adrenoceptors, whereas in the distal colon, both alpha- and beta-adrenoceptors are involved, as shown by the sensitivity against, e.g. phentolamine and propranolol. These adrenoceptors seem to be located - at least in part - at extraepithelial sites because the (1) phase of the norepinephrine response was sensitive to indomethacin, and the (2) phase, both to indomethacin and tetrodotoxin.