Adrenoceptor-mediated secretion across the rat colonic epithelium

Norepinephrine evoked a biphasic change in short-circuit current (Isc) acro ss the proximal and distal colon of the rat. The (1) phase of the current r esponse consisted of a transient increase, which was followed by a long-las ting decrease during the (2) phase. The (1)phase, which is assumed to repre sent Cl- secretion, was resistant against classical adrenoceptor antagonist s, but was inhibited by the beta(3)-adrenoceptor antagonist 3-(2-ethylpenox y)-1-[(1S-1,2,3,4-tetrahydronaphth-1-ylaminol-(2S)propranol oxalate (SR 592 30A) in the proximal colon and by the non-selective beta-adrenoceptor antag onist 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]phenoxyacetic acid (BRL 37344). The (2) phase of the norepinephrine-induced Isc, which is assumed to repre sent K+ secretion, was inhibited by yohimbine in the proximal colon, sugges ting the mediation by alpha(2)-adrenoceptors, whereas in the distal colon, both alpha- and beta-adrenoceptors are involved, as shown by the sensitivit y against, e.g. phentolamine and propranolol. These adrenoceptors seem to b e located - at least in part - at extraepithelial sites because the (1) pha se of the norepinephrine response was sensitive to indomethacin, and the (2 ) phase, both to indomethacin and tetrodotoxin. (C) 2000 Elsevier Science B .V. All rights reserved.