uroguanylin and Cystic-Fibrosis

uroguanylin has been researched along with Cystic-Fibrosis* in 2 studies

Other Studies

2 other study(ies) available for uroguanylin and Cystic-Fibrosis

ArticleYear
Meconium ileus caused by mutations in GUCY2C, encoding the CFTR-activating guanylate cyclase 2C.
    American journal of human genetics, 2012, May-04, Volume: 90, Issue:5

    Meconium ileus, intestinal obstruction in the newborn, is caused in most cases by CFTR mutations modulated by yet-unidentified modifier genes. We now show that in two unrelated consanguineous Bedouin kindreds, an autosomal-recessive phenotype of meconium ileus that is not associated with cystic fibrosis (CF) is caused by different homozygous mutations in GUCY2C, leading to a dramatic reduction or fully abrogating the enzymatic activity of the encoded guanlyl cyclase 2C. GUCY2C is a transmembrane receptor whose extracellular domain is activated by either the endogenous ligands, guanylin and related peptide uroguanylin, or by an external ligand, Escherichia coli (E. coli) heat-stable enterotoxin STa. GUCY2C is expressed in the human intestine, and the encoded protein activates the CFTR protein through local generation of cGMP. Thus, GUCY2C is a likely candidate modifier of the meconium ileus phenotype in CF. Because GUCY2C heterozygous and homozygous mutant mice are resistant to E. coli STa enterotoxin-induced diarrhea, it is plausible that GUCY2C mutations in the desert-dwelling Bedouin kindred are of selective advantage.

    Topics: Amino Acid Sequence; Animals; Bacterial Toxins; Cyclic GMP; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Diarrhea; Down-Regulation; Enterotoxins; Escherichia coli Proteins; Female; Gastrointestinal Hormones; Genes, Modifier; HEK293 Cells; Heterozygote; Humans; Intestinal Mucosa; Intestinal Obstruction; Male; Meconium; Mice; Molecular Sequence Data; Mutation; Natriuretic Peptides; Pedigree; Phenotype; Receptors, Enterotoxin; Receptors, Guanylate Cyclase-Coupled; Receptors, Peptide

2012
Heat-stable enterotoxin of Escherichia coli stimulates a non-CFTR-mediated duodenal bicarbonate secretory pathway.
    American journal of physiology. Gastrointestinal and liver physiology, 2005, Volume: 288, Issue:4

    The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is an important pathway for duodenal mucosal bicarbonate secretion. Duodenal biopsies from CF patients secrete bicarbonate in response to heat-stable enterotoxin from Escherichia coli (STa) but not cAMP. To explore the mechanism of STa-induced bicarbonate secretion in CF more fully, we examined the role of CFTR in STa-stimulated duodenal bicarbonate secretion in mice. In vivo, the duodenum of CFTR (-/-) or control mice was perfused with forskolin (10(-4) M), STa (10(-7) M), uroguanylin (10(-7) M), 8-bromoguanosine 3',5'-cGMP (8-Br-cGMP) (10(-3) M), genistein (10(-6) M) plus STa, or herbimycin A (10(-6) M) plus STa. In vitro, duodenal mucosae were voltage-clamped in Ussing chambers, and bicarbonate secretion was measured by pH-stat. The effect of genistein, DIDS (10(-4) M), and chloride removal was also studied in vitro. Control, but not CF, mice produced a significant increase in duodenal bicarbonate secretion after perfusion with forskolin, uroguanylin, or 8-Br-cGMP. However, both control and CF animals responded to STa with significant increases in bicarbonate output. Genistein and herbimycin A abolished this response in CF mice but not in controls. In vitro, STa-stimulated bicarbonate secretion in CF tissues was inhibited by genistein, DIDS, and chloride-free conditions, whereas bicarbonate secretion persisted in control mice. In the CF duodenum, STa can stimulate bicarbonate secretion via tyrosine kinase activity resulting in apical Cl(-)/HCO(3)(-) exchange. Further studies elucidating the intracellular mechanisms responsible for such non-CFTR mediated bicarbonate secretion may lead to important therapies for CF.

    Topics: Animals; Bacterial Toxins; Benzoquinones; Bicarbonates; Cell Membrane; Chloride-Bicarbonate Antiporters; Colforsin; Cyclic GMP; Cystic Fibrosis; Duodenum; Enterotoxins; Enzyme Inhibitors; Escherichia coli Proteins; Genistein; In Vitro Techniques; Lactams, Macrocyclic; Mice; Natriuretic Peptides; Peptides; Protein-Tyrosine Kinases; Quinones; Rifabutin

2005