cyclic-gmp and 3-((3-trifluoromethyl)phenyl)-5-((3-carboxyphenyl)methylene)-2-thioxo-4-thiazolidinone

cyclic-gmp has been researched along with 3-((3-trifluoromethyl)phenyl)-5-((3-carboxyphenyl)methylene)-2-thioxo-4-thiazolidinone* in 1 studies

Other Studies

1 other study(ies) available for cyclic-gmp and 3-((3-trifluoromethyl)phenyl)-5-((3-carboxyphenyl)methylene)-2-thioxo-4-thiazolidinone

Article	Year
Prevention of toxin-induced intestinal ion and fluid secretion by a small-molecule CFTR inhibitor. Gastroenterology, 2004, Volume: 126, Issue:2 The cystic fibrosis transmembrane conductance regulator (CFTR) provides an important apical route for Cl(-) secretion across intestinal epithelia. A thiazolidinone-type CFTR blocker (CFTR(inh)-172) reduced cholera toxin-induced fluid accumulation in mouse intestinal loops. Here, we characterize the efficacy and pharmacodynamics of CFTR(inh)-172 in blocking cAMP and cGMP induced Cl(-)/fluid secretion in rodent and human intestine.. CFTR(inh)-172 inhibited cAMP and cGMP agonist induced short-circuit current by >95% in T84 colonic epithelial cells (K(I) approximately 3 micromol/L) and in mouse and human intestinal sheets (K(I) approximately 9 micromol/L). A single intraperitoneal injection of CFTR(inh)-172 (200 microg) blocked intestinal fluid secretion in a rat closed-loop model by >90% for cholera toxin and >70% for STa Escherichia coli toxin. In mice, CFTR(inh)-172 (20 microg) inhibited cholera toxin-induced intestinal fluid secretion by 90% (persistence t(1/2) approximately 10 hours, K(I) approximately 5 microg) and STa toxin by 75% (K(I) approximately 10 microg). Tissue distribution and pharmacokinetic studies indicated intestinal CFTR(inh)-172 accumulation facilitated by enterohepatic circulation. An oral CFTR(inh)-172 preparation reduced fluid secretion by >90% in a mouse open-loop cholera model.. A small molecule CFTR blocker markedly reduced intestinal ion and fluid secretion caused by cAMP/cGMP-dependent bacterial enterotoxins. CFTR inhibition may thus reduce fluid secretion in infectious secretory diarrheas. Topics: Administration, Oral; Animals; Bacterial Toxins; Benzoates; Body Fluids; Cell Line; Chlorides; Cholera Toxin; Cyclic AMP; Cyclic GMP; Electric Conductivity; Enterotoxins; Escherichia coli Proteins; Humans; Injections, Intraperitoneal; Intestinal Mucosa; Intestines; Ion Channels; Male; Mice; Mice, Inbred Strains; Mice, Mutant Strains; Rats; Rats, Wistar; Thiazoles; Thiazolidines; Tissue Distribution	2004

Article

Year

Prevention of toxin-induced intestinal ion and fluid secretion by a small-molecule CFTR inhibitor.

Gastroenterology, 2004, Volume: 126, Issue:2

The cystic fibrosis transmembrane conductance regulator (CFTR) provides an important apical route for Cl(-) secretion across intestinal epithelia. A thiazolidinone-type CFTR blocker (CFTR(inh)-172) reduced cholera toxin-induced fluid accumulation in mouse intestinal loops. Here, we characterize the efficacy and pharmacodynamics of CFTR(inh)-172 in blocking cAMP and cGMP induced Cl(-)/fluid secretion in rodent and human intestine.. CFTR(inh)-172 inhibited cAMP and cGMP agonist induced short-circuit current by >95% in T84 colonic epithelial cells (K(I) approximately 3 micromol/L) and in mouse and human intestinal sheets (K(I) approximately 9 micromol/L). A single intraperitoneal injection of CFTR(inh)-172 (200 microg) blocked intestinal fluid secretion in a rat closed-loop model by >90% for cholera toxin and >70% for STa Escherichia coli toxin. In mice, CFTR(inh)-172 (20 microg) inhibited cholera toxin-induced intestinal fluid secretion by 90% (persistence t(1/2) approximately 10 hours, K(I) approximately 5 microg) and STa toxin by 75% (K(I) approximately 10 microg). Tissue distribution and pharmacokinetic studies indicated intestinal CFTR(inh)-172 accumulation facilitated by enterohepatic circulation. An oral CFTR(inh)-172 preparation reduced fluid secretion by >90% in a mouse open-loop cholera model.. A small molecule CFTR blocker markedly reduced intestinal ion and fluid secretion caused by cAMP/cGMP-dependent bacterial enterotoxins. CFTR inhibition may thus reduce fluid secretion in infectious secretory diarrheas.

Topics: Administration, Oral; Animals; Bacterial Toxins; Benzoates; Body Fluids; Cell Line; Chlorides; Cholera Toxin; Cyclic AMP; Cyclic GMP; Electric Conductivity; Enterotoxins; Escherichia coli Proteins; Humans; Injections, Intraperitoneal; Intestinal Mucosa; Intestines; Ion Channels; Male; Mice; Mice, Inbred Strains; Mice, Mutant Strains; Rats; Rats, Wistar; Thiazoles; Thiazolidines; Tissue Distribution

2004