A novel plant-derived inhibitor of cAMP-mediated fluid and chloride secretion
| Autor: | Sherif E. Gabriel, V. Vimal, R. J. Steagall, E. J. Rozhon, T. Carlson, S. E. Davenport |
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| Rok vydání: | 1999 |
| Předmět: |
Male
Cholera Toxin medicine.medical_specialty Physiology Pharmacology medicine.disease_cause Catechin Drug Administration Schedule Cell Line Mice Biopolymers Chlorides In vivo Physiology (medical) Internal medicine Intestine Small Cyclic AMP Electric Impedance medicine Animals Humans Secretion Dose-Response Relationship Drug Hepatology biology Colforsin Cholera toxin Electric Conductivity Gastroenterology medicine.disease Cholera In vitro Cystic fibrosis transmembrane conductance regulator Body Fluids Mice Inbred C57BL Endocrinology Cell culture biology.protein Chloride channel Female Caco-2 Cells |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 276:G58-G63 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.1999.276.1.g58 |
| Popis: | We have identified an agent (SP-303) that shows efficacy against in vivo cholera toxin-induced fluid secretion and in vitro cAMP-mediated Cl−secretion. Administration of cholera toxin to adult mice results in an increase in fluid accumulation (FA) in the small intestine (FA ratio = 0.63 vs. 1.86 in control vs. cholera toxin-treated animals, respectively). This elevation in FA induced by cholera toxin was significantly reduced (FA ratio = 0.70) in animals treated with a 100 mg/kg dose of SP-303 at the same time as the cholera treatment. Moreover, when SP-303 was administered 3 h after cholera toxin, a dose-dependent inhibition of FA levels was observed with a half-maximal inhibitory dose of 10 mg/kg. In Ussing chamber studies of Caco-2 or T84 monolayer preparations, SP-303 had a significant effect on both basal current and forskolin-stimulated Cl−current. SP-303 also induced an increase in resistance that paralleled the observed decrease in current. These data suggest that SP-303 has an inhibitory effect on cAMP-mediated Cl−and fluid secretion. Thus SP-303 may prove to be a useful broad-spectrum antidiarrheal agent. |
| Databáze: | OpenAIRE |
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