Molecular biology of Na+ absorption.
Aldosterone controls the activity of the amiloride-sensitive epithelial Na+ channel located in the apical membrane of epithelial cells from the distal colon and kidney collecting duct. This channel is a key element in the antinatriuretic response to aldosterone. It consists of three homologous subunits, alpha-ENaC, beta-ENaC, and gamma-ENaC (for epithelial Na+ channel), which share significant identity with degenerins, a family of proteins found in the nematode Caenorhabditis elegans, and with ligand-gated cation channels, such as FaNaC [Phe-Met-Arg-Phe-NH2 (i.e., FMRF-amide) Na+ channel] or ASIC (acid-sensing ion channel), two neuronal ionotropic receptors for Phe-Met-Arg-Phe-NH2 and H+, respectively. All of these proteins contain a large extracellular loop located between two large hydrophobic domains. The NH2- and COOH-terminal domains are cytoplasmic and contain potential regulatory motifs. Gain-of-function mutations affecting beta-ENaC and gamma-ENaC genes can cause Liddle syndrome, a rare from of genetic hypertension. Loss-of-function mutations affecting alpha-ENaC or beta-ENaC genes can cause pseudohypoaldosteronism type 1. Steroids strongly increase beta-ENaC and gamma-ENaC transcription in rat distal colon. A different situation is observed in rat kidney, in which the large stimulation of ENaC activity is mainly via posttranslational mechanisms. In both tissues, aldosterone increases cell surface expression of the ENaC subunits.
Barbry
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Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique Unité Propre de Recherche 411, Valbonne, France.
Hofman
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D000450:Aldosterone / Q000502:physiology; D000595:Amino Acid Sequence; D000802:Angiotensin Amide / Q000235:genetics / Q000502:physiology; D000818:Animals; D003106:Colon / Q000502:physiology*; D004848:Epithelium / Q000502:physiology; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000502:physiology*; D007685:Kidney Tubules, Collecting / Q000502:physiology; D008969:Molecular Sequence Data; D010802:Phylogeny; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*
D015222:Sodium Channels; D000450:Aldosterone; D000802:Angiotensin Amide; D012964:Sodium