Article date: May 2017
By: Sandra Bader, Lena Lottig, Martin Diener in Volume 174, Issue 9, pages 880-892
Background and Purpose
Acetylcholine‐induced epithelial Cl− secretion is generally thought to be mediated by epithelial muscarinic receptors and nicotinic receptors on secretomotor neurons. However, recent data have shown expression of nicotinic receptors by intestinal epithelium and the stimulation of Cl− secretion by nicotine, in the presence of the neurotoxin, tetrodotoxin. Here, we aimed to identify the transporters activated by epithelial nicotinic receptors and to clarify their role in cholinergic regulation of intestinal ion transport.
Experimental Approach
Ussing chamber experiments were performed, using rat distal colon with intact epithelia. Epithelia were basolaterally depolarized to measure currents across the apical membrane. Apically permeabilized tissue was also used to measure currents across the basolateral membrane in the presence of tetrodotoxin.
Key Results
Nicotine had no effect on currents through Cl− channels in the apical membrane or on currents through K+ channels in the apical or the basolateral membrane. Instead, nicotine stimulated the Na+‐K+‐pump as indicated by Na+‐dependency and sensitivity of the nicotine‐induced current across the basolateral membrane to cardiac steroids. Effects of nicotine were inhibited by nicotinic receptor antagonists such as hexamethonium and mimicked by dimethyl‐4‐phenylpiperazinium, a chemically different nicotinic agonist. Simultaneous stimulation of epithelial muscarinic and nicotinic receptors led to a strong potentiation of transepithelial Cl− secretion.
Conclusions and Implications
These results suggest a novel concept for the cholinergic regulation of transepithelial ion transport by costimulation of muscarinic and nicotinic epithelial receptors and a unique role of nicotinic receptors controlling the activity of the Na+‐K+‐ATPase.
DOI: 10.1111/bph.13761
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