H 2 S is a key antisecretory molecule against cholera toxin-induced diarrhoea in mice: Evidence for non-involvement of the AC/cAMP/PKA pathway and AMPK

• Published in: Nitric oxide Vol. 76; p. 152
• Main Authors: Sousa, Francisca B M, Souza, Luan K M, Sousa, Nayara A, Araújo, Thiago S L, de Araújo, Simone, Pacífico, Dvison M, Silva, Irismara S, Silva, Renan O, Nicolau, Lucas A D, Souza, Fabiana M, Filgueiras, Marcelo C, Oliveira, Jefferson S, Souza, Marcellus H L P, Medeiros, Jand Venes R
• Format: Journal Article
• Language: English
• Published: United States 01.06.2018
• Subjects: Gaseous mediators; AMPK; Cholera; Diarrhea diseases
• ISSN: 1089-8611
• DOI: 10.1016/j.niox.2017.09.007

Hydrogen sulphide (H S) is a gasotransmitter that participates in various physiological and pathophysiological processes within the gastrointestinal tract. We studied the effects and possible mechanism of action of H S in secretory diarrhoea caused by cholera toxin (CT). The possible mechanisms of action of H S were investigated using an intestinal fluid secretion model in isolated intestinal loops on anaesthetized mice treated with CT. NaHS and Lawesson's reagent and l-cysteine showed antisecretory activity through reduction of intestinal fluid secretion and loss of Cl induced by CT. Pretreatment with an inhibitor of cystathionine-γ-lyase (CSE), dl-propargylglycine (PAG), reversed the effect of l-cysteine and caused severe intestinal secretion. Co-treatment with PAG and a submaximal dose of CT increased intestinal fluid secretion, thus supporting the role of H S in the pathophysiology of cholera. CT increased the expression of CSE and the production of H S. Pretreatment with PAG did not reverse the effect of SQ 22536 (an AC inhibitor), bupivacaine (inhibitor of cAMP production), KT-5720 (a PKA inhibitor), and AICAR (an AMPK activator). The treatment with Forskolin does not reverse the effects of the H S donors. Co-treatment with either NaHS or Lawesson's reagent and dorsomorphin (an AMPK inhibitor) did not reverse the effect of the H S donors. H S has antisecretory activity and is an essential molecule for protection against the intestinal secretion induced by CT. Thus, H S donor drugs are promising candidates for cholera therapy. However, more studies are needed to elucidate the possible mechanism of action.