Antisecretory factor peptide derivatives specifically inhibit [3H]-gamma-amino-butyric acid/36Cl- out-->in permeation across the isolated rabbit Deiters' neuronal membrane

Acta Physiol Scand. 2003 Dec;179(4):367-71. doi: 10.1111/j.1365-201X.2003.01173.x.

Abstract

Aims: Antisecretory factor (AF) is a 41-kDa protein, its main function being the regulation of intestinal ion/water transport, but it also inhibits chloride and gamma-amino-butyric acid transport across nerve cell membranes. The present experiments were designed to evaluate whether the same AF peptide sequence mediates the permeability effects seen at the nerve cell membrane and in the rat small intestine.

Methods: Four peptides were prepared by the solid phase technique with sequences derived from positions 1-51 of the full-length antisecretory factor AF and tested on nerve cell membranes isolated from rabbit Dieter cells.

Results: AF peptides containing the active 36-51 peptide exerted a blocking effect of the out-->in permeation of 36Cl- as well as of [3H]-gamma-amino-butyric acid. The minimal dose causing inhibition, however, varied between 10(-11) m (AF10) and 10(-7) m (AF13). The most potent peptides have been shown previously to be active in inhibiting experimental diarrhoea in vivo in small intestinal ligated loops in rats. The non-active sequence AF23-32 did not inhibit any of the two permeation markers in vitro, a result which supports the lack of activity found also in vivo.

Conclusion: The results suggest that AF, or AF derivatives, counteract intestinal hypersecretion by blocking anion permeation across large anionic pores. Such a blocking effect could also influence the generation of action potentials in enteric nerve cells controlling the intestinal water and ion transport system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Membrane Permeability / physiology
  • Chloride Channels / metabolism
  • Chlorides / metabolism*
  • Intestine, Small / metabolism
  • Male
  • Neurons / metabolism*
  • Neuropeptides / metabolism*
  • Peptide Fragments / metabolism
  • Rabbits
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Chloride Channels
  • Chlorides
  • Neuropeptides
  • Peptide Fragments
  • antisecretory factor
  • gamma-Aminobutyric Acid