Chloride secretion in response to guanylin in colonic epithelial from normal and transgenic cystic fibrosis mice
| Autor: | Alan W. Cuthbert, M. E. Hickman, Mathew J. Evans, William H. Colledge, P.W. Seale, P.P.A. Humphrey, Rosemary Ratcliff, L J MacVinish |
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| Rok vydání: | 1994 |
| Předmět: |
medicine.medical_specialty
Heterozygote Cystic Fibrosis Colon Guanylin Bacterial Toxins Molecular Sequence Data Cystic Fibrosis Transmembrane Conductance Regulator Mice Transgenic In Vitro Techniques Cystic fibrosis Epithelium Gastrointestinal Hormones chemistry.chemical_compound Enterotoxins Mice Intestinal mucosa Chlorides Isomerism Chloride Channels Internal medicine medicine Heat-stable enterotoxin Animals Amino Acid Sequence Intestinal Mucosa Receptor Natriuretic Peptides Pharmacology biology Escherichia coli Proteins Membrane Proteins medicine.disease Molecular biology Cystic fibrosis transmembrane conductance regulator Mice Inbred C57BL Endocrinology chemistry biology.protein Chloride channel Peptides hormones hormone substitutes and hormone antagonists Uroguanylin Research Article |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0007-1188 |
| Popis: | 1. Guanylin, a 15 amino acid endogenous gut peptide, increased the short circuit current (SCC) in the epithelium of the mouse colon, but only when applied to the apical and not the basolateral surface. 2. By use of selective blockers of epithelial ion transport and modification of the bathing solution, it was concluded that guanylin increased electrogenic chloride secretion but also had a minor effect on electrogenic sodium absorption. In addition there were small residual currents which remained unresolved. 3. The threshold concentration of guanylin causing a SCC increase was less than 50 nM, but at concentrations 40 times greater no indication of a maximally effective concentration was found. 4. Two guanylin isomers with the same amino acid sequence but with the disulphide bridges joined in an alternate fashion showed no activity. Thus only guanylin with the greatest structural homology to heat stable enterotoxin (STa) showed biological activity. 5. The action of guanylin was virtually eliminated in colonic epithelia from transgenic cystic fibrosis (CF) mice. As these animals lack the chloride channel coded by the CF gene sequence, it is likely that the final effector process in murine colonic epithelia involves the CFTR (cystic fibrosis transmembrane conductance regulator) chloride channel. 6. Opportunistic infections of the gut generating STa lead to diarrhoeal conditions via an action of the toxin on apical guanylin receptors. Thus, as discussed, the CF heterozygote may have a genetic advantage in this circumstance. |
| Databáze: | OpenAIRE |
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