Adrenoceptor-mediated secretion across the rat colonic epithelium

Abstract

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 β 3-adrenoceptor antagonist 3-(2-ethylpenoxy)-1-[(1 S-1,2,3,4-tetrahydronaphth-1-ylaminol-(2 S)-propranol oxalate (SR 59230A) in the proximal colon and by the non-selective β-adrenoceptor antagonist bupranolol in both colonic segments. Vice versa, the increase in Isc was mimicked by the β 3-adrenoceptor agonist, ( R*, R*)-(±)-4-[2-[(2-(3-chlorophenyl)-2-hydroxyethyl)amino]propyl]phenoxyacetic 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 α 2-adrenoceptors, whereas in the distal colon, both α- and β-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.