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.
Schultheiss
G
G
Institut für Veterinär-Physiologie, Justus-Liebig-Universität Giessen, Frankfurter Str. 100, D-35392, Giessen, Germany. gerhard.schultheiss@vetmed.un-giessen.de
Diener
M
M
D000818:Animals; D003106:Colon / Q000378:metabolism*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects / Q000378:metabolism
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D009638:Norepinephrine