H2S is a key antisecretory molecule against cholera toxin-induced diarrhoea in mice: Evidence for non-involvement of the AC/cAMP/PKA pathway and AMPK
| Autor: | Jand Venes R. Medeiros, Francisca Beatriz M. Sousa, Thiago S.L. Araújo, Jefferson Soares de Oliveira, Luan Kelves Miranda de Souza, Simone de Araújo, Marcellus H.L.P. Souza, Lucas A.D. Nicolau, Dvison M. Pacífico, Fabiana de Moura Souza, Marcelo de Carvalho Filgueiras, Renan O. Silva, Nayara A. Sousa, Irismara Sousa Silva |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research medicine.medical_specialty Physiology Clinical Biochemistry medicine.disease_cause Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Secretion Gastrointestinal tract Forskolin Activator (genetics) Cholera toxin AMPK equipment and supplies Pathophysiology 030104 developmental biology Endocrinology Mechanism of action chemistry 030220 oncology & carcinogenesis medicine.symptom |
| Zdroj: | Nitric Oxide. 76:152-163 |
| ISSN: | 1089-8603 |
| Popis: | Hydrogen sulphide (H2S) 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 H2S in secretory diarrhoea caused by cholera toxin (CT). The possible mechanisms of action of H2S 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 H2S in the pathophysiology of cholera. CT increased the expression of CSE and the production of H2S. 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 H2S donors. Co-treatment with either NaHS or Lawesson's reagent and dorsomorphin (an AMPK inhibitor) did not reverse the effect of the H2S donors. H2S has antisecretory activity and is an essential molecule for protection against the intestinal secretion induced by CT. Thus, H2S donor drugs are promising candidates for cholera therapy. However, more studies are needed to elucidate the possible mechanism of action. |
| Databáze: | OpenAIRE |
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