Journal article

Publication year: 2017

Pages: 880-892

Journal: British Journal of Pharmacology

Volume number: 174

Issue number: 9

ISSN: 0007-1188

eISSN: 1476-5381

Open access status: Green

DOI Link: https://doi.org/10.1111/bph.13761

Publisher: Wiley

Abstract: 

Background and PurposeAcetylcholine-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 ApproachUssing 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 ResultsNicotine 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 ImplicationsThese 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.

Harvard Citation style: Bader, S., Lottig, L. and Diener, M. (2017) Stimulation of Na+-K+-pump currents by epithelial nicotinic receptors in rat colon, British Journal of Pharmacology, 174(9), pp. 880-892. https://doi.org/10.1111/bph.13761

APA Citation style: Bader, S., Lottig, L., & Diener, M. (2017). Stimulation of Na+-K+-pump currents by epithelial nicotinic receptors in rat colon. British Journal of Pharmacology. 174(9), 880-892. https://doi.org/10.1111/bph.13761