Journal article

Publication year: 2011

Pages: 392-404

Journal: British Journal of Pharmacology

Volume number: 162

Issue number: 2

ISSN: 0007-1188

eISSN: 1476-5381

Open access status: Green

DOI Link: https://doi.org/10.1111/j.1476-5381.2010.01026.x

Publisher: Wiley

Abstract: 

BACKGROUND AND PURPOSE

The aim of this study was to clarify the mechanisms by which hydrogen sulphide (H2S) affects ion secretion across rat distal colonic epithelium.

EXPERIMENTAL APPROACH

Changes in short-circuit current induced by the H2S-donor, sodium hydrosulphide (NaHS; 10 mmol center dot L-1), were measured in Ussing chambers after permeabilization of the apical membrane with nystatin. Cytosolic Ca2+ concentration ([Ca2+](i)) and Ca2+ in intracellular stores were measured with fluorescent dyes. Changes in mitochondrial membrane potential were estimated with rhodamine 123.

KEY RESULTS

NaHS had a biphasic effect on overall currents across the basolateral membrane: an initial inhibition followed by a secondary stimulation. Both a scilliroside-sensitive action on the Na+-K+-ATPase and modulation of glibenclamide-sensitive and tetrapentylammonium-sensitive (i.e. ATP-sensitive and Ca2+-dependent) basolateral K+ channels were involved in this action. Experiments with rhodamine 123 revealed that NaHS induced a hyperpolarization of the mitochondrial membrane. NaHS evoked a biphasic change in [Ca2+](i), an initial decrease followed by a secondary increase, known to be mediated by the release of stored Ca2+. Initial falls in [Ca2+](i) were not mediated by a sequestration of Ca2+ in intracellular Ca2+ storing organelles, as the Mag-Fura-2 signal was unaffected by NaHS. Falls in [Ca2+](i) were inhibited by 2',4'-dichlorobenzamil, an inhibitor of the Na+-Ca2+-exchanger, and attenuated in Na+-free buffer, suggesting a transient stimulation of Ca2+ outflow by this transporter, directly demonstrated by Mn2+ quenching experiments.

CONCLUSIONS AND IMPLICATIONS

ATP-sensitive and Ca2+-dependent basolateral K+ conductances, the basolateral Na+-K+-pump as well as Ca2+ transporters were involved in the action of H2S in regulating colonic ion secretion.

Harvard Citation style: Pouokam, E. and Diener, M. (2011) Mechanisms of actions of hydrogen sulphide on rat distal colonic epithelium, British Journal of Pharmacology, 162(2), pp. 392-404. https://doi.org/10.1111/j.1476-5381.2010.01026.x

APA Citation style: Pouokam, E., & Diener, M. (2011). Mechanisms of actions of hydrogen sulphide on rat distal colonic epithelium. British Journal of Pharmacology. 162(2), 392-404. https://doi.org/10.1111/j.1476-5381.2010.01026.x