Epithelial muscarinic M1 receptors contribute to carbachol-induced ion secretion in mouse colon.
Cholinergically induced intestinal anion secretion is generally believed to be caused by stimulation of epithelial muscarinic M3 receptors, whereas muscarinic M1 receptors are thought to be localized primarily on enteric neurons. In order to test this assumption, carbachol-stimulated Cl- secretion across distal colon, measured as increase in short-circuit current (I(sc)), was compared between M1-knockout (M1R-KO) and M3-knockout (M3R-KO) mice. Surprisingly, the maximal increase in I(sc) evoked by carbachol was more than twice as large in M3R-KO compared to M1R-KO mice. This difference was not due to a reduced secretory capacity of the epithelium from M3R-KO animals, as forskolin stimulated a similar maximal I(sc) in both types of animals. The neurotoxin tetrodotoxin diminished, but did not abolish the secretory response evoked by carbachol in M3R-KO distal colon, suggesting the existence of epithelial muscarinic receptors other than the type M3. Furthermore, in muscarinic receptor wild-type animals, the muscarinic M1 receptor antagonist pirenzepine inhibited the carbachol-stimulated I(sc) by more than 70% suggesting the presence of epithelial muscarinic M1 receptors; a conclusion, which was confirmed by the identification of mRNA for muscarinic M1 receptors in isolated crypts from wild-type colon. Consequently, epithelial muscarinic receptors from the type M1 contribute to cholinergically induced ion secretion in mouse colon.
Haberberger
Rainer
R
Institut für Anatomie und Zellbiologie, Justus-Liebig-Universität Giessen, D-35392 Giessen, Germany.
Schultheiss
Gerhard
G
Diener
Martin
M
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D018679:Cholinergic Agonists / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D043643:Receptor, Muscarinic M1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D043587:Receptor, Muscarinic M3 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
D002712:Chlorides; D018679:Cholinergic Agonists; D012333:RNA, Messenger; D043643:Receptor, Muscarinic M1; D043587:Receptor, Muscarinic M3; D002217:Carbachol