Elsevier

Biochimie

Volume 70, Issue 9, September 1988, Pages 1285-1290
Biochimie

Amiloride and its analogs as tools to inhibit Na+ transport via the Na+ channel, the Na+/H+ antiport and the Na+/Ca2+ exchanger

https://doi.org/10.1016/0300-9084(88)90196-4Get rights and content

Abstract

Amiloride analogs inhibit a number of transmembrane Na+ transport systems: 1) the epithelium Na+ channel, 2) the Na+/H+ exchange system and 3) the Na+/Ca2+ exchange system. Structure-activity relationships using amiloride derivatives with selected modification of each of the functional groups of the molecule indicate that the 3 Na+ transporting systems have distinct pharmacological profiles. 5-N Disubstituted derivatives of amiloride, such as ethylisopropylamiloride are the most potent inhibitors of the Na+/H+ exchange system. Conversely, amiloride derivatives that are substituted on the guanidino moiety, such as phenamil, are potent inhibitors of the epithelium Na+ channel. It is thus possible, by using selected amiloride derivatives to inhibit selectively one or another of the Na+ transport systems.

References (31)

  • P. Barbry et al.

    Biochem. Biophys. Res. Commun.

    (1986)
  • M. Lazdunski et al.

    J. Mol. Cell. Cardiol.

    (1985)
  • P. Vigne et al.

    Biochem. Biophys. Res. Commun.

    (1983)
  • G. L'Allemain et al.

    J. Biol. Chem.

    (1984)
  • C. Frelin et al.

    J. Biol. Chem.

    (1984)
  • J.F. Besterman et al.

    J. Biol. Chem.

    (1985)
  • P. Vigne et al.

    J. Biol. Chem.

    (1985)
  • T.R. Kleyman et al.

    J. Biol. Chem.

    (1986)
  • D.J. Benos

    Am. J. Physiol.

    (1982)
  • B. Lindemann

    Annu. Rev. Physiol.

    (1984)
  • A.W. Cuthbert et al.

    Br. J. Pharmacol.

    (1978)
  • J.H.Y. Li et al.

    J. Membr. Biol.

    (1985)
  • D.J. Benos et al.

    J. Gen. Physiol.

    (1976)
  • R.G. O'Neil et al.

    J. Membr. Biol.

    (1979)
  • J.L. Garvin et al.

    J. Membr. Biol.

    (1985)
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