Journalartikel

Jahr der Veröffentlichung: 2013

Seiten: 133-141

Zeitschrift: European Journal of Pharmacology

Bandnummer: 715

Heftnummer: 1-3

ISSN: 0014-2999

eISSN: 1879-0712

DOI Link: https://doi.org/10.1016/j.ejphar.2013.05.031

Verlag: Elsevier

Abstract: 

The aim of this study was to investigate whether nitroxyl (HNO), a redox variant of the radical gasotransmitter nitric oxide (NO) with therapeutically promising properties, affects colonic ion transport. Changes in short-circuit current (I-SC) induced by the HNO donor Angeli's salt were recorded in Listing chambers. Cytosolic Ca2+ concentration was measured with fura-2. The nitroxyl donor induced a concentration-dependent increase in ISC across rat distal colon which was due to a stimulation of chloride secretion. The secretion induced by Angelis salt (5 x 10(-4) mol/l) was not altered by the NO scavenger 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3-oxide (carboxy-PTIO), but was abolished by the HNO scavenger L-cysteine. The response was not dependent on the activity of soluble guanylate cyclase or enteric neurons, but was inhibited by indomethacin. Experiments with apically permeabilized epithelia revealed the activation of basolateral K+ channels and a stimulation of the current carried by the basolateral Na+-K+-pump by Angeli's salt. The secretion induced by Angeli's salt was reduced in the absence of extracellular Ca2+. A prominent increase in the cytosolic Ca2+ concentration was evoked by Angeli's salt predominantly in subepithelial cells within the submucosa, which had the same dependence on extracellular Ca2+ as the Angeli's salt-induced Cl- secretion. Consequently, Angeli's salt induces a soluble guanylate cyclase-independent, Ca2+-dependent Cl- secretion via activation of the Na+-K+-ATPase and of basolateral K+ channels. Cyclooxygenase metabolites produced within the submucosa seem to be involved in this response.

Harvard-Zitierstil: Pouokam, E., Bell, A. and Diener, M. (2013) Actions of Angeli's salt, a nitroxyl (HNO) donor, on ion transport across mucosa-submucosa preparations from rat distal colon, European Journal of Pharmacology, 715(1-3), pp. 133-141. https://doi.org/10.1016/j.ejphar.2013.05.031

APA-Zitierstil: Pouokam, E., Bell, A., & Diener, M. (2013). Actions of Angeli's salt, a nitroxyl (HNO) donor, on ion transport across mucosa-submucosa preparations from rat distal colon. European Journal of Pharmacology. 715(1-3), 133-141. https://doi.org/10.1016/j.ejphar.2013.05.031