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Diabetes Insipidus, Molecular Biology of

Molecular Biology of Specific Diseases

  1. Alexander Oksche1,2,
  2. Peter Pohl2,
  3. Gerd Krause2,
  4. Walter Rosenthal1,2

Published Online: 15 SEP 2006

DOI: 10.1002/3527600906.mcb.200300072

Reviews in Cell Biology and Molecular Medicine

Reviews in Cell Biology and Molecular Medicine

How to Cite

Oksche, A., Pohl, P., Krause, G. and Rosenthal, W. 2006. Diabetes Insipidus, Molecular Biology of. Reviews in Cell Biology and Molecular Medicine. .

Author Information

  1. 1

    Institut für Pharmakologie, Charité–Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany

  2. 2

    Forschungsinstitut für Molekulare Pharmakologie, Berlin, Germany

Publication History

  1. Published Online: 15 SEP 2006

Abstract

The neurohypophyseal hormone vasopressin acts via three different G protein-coupled receptors. The main physiological response elicited by vasopressin is antidiuresis, which is mediated by vasopressin V2 receptors in the kidney. Further responses, such as vasoconstriction and the release of the adrenocorticotropic hormone (ACTH), are mediated by vasopressin V1a and vasopressin V1b receptors respectively.

Diabetes insipidus is a hereditary or acquired disease characterized by polyuria and polydipsia. It is either caused by an insufficient release of vasopressin from the neurohypophysis (central diabetes insipidus) or by a resistance of the kidney toward the action of vasopressin (nephrogenic diabetes insipidus).

In the case of central diabetes insipidus, autosomal dominant and autosomal recessive modes of inheritance are known. In both traits, mutations in the vasopressin-neurophysin II gene (encodes the vasopressin precursor) are responsible for the disease. For congenital nephrogenic diabetes insipidus, three modes of inheritance are known: X-chromosomal recessive, autosomal recessive, and autosomal dominant. While the X-chromosomal trait is caused by mutations in the vasopressin V2 receptor gene, the autosomal forms are due to mutations in the aquaporin-2 gene (encodes the vasopressin-regulated water channel).

Analysis of mutant vasopressin-neurophysin II, vasopressin V2 receptor, and aquaporin-2 proteins revealed impaired protein transport as the most common cause of the disease. The transport defect is either caused by (1) retention of misfolded proteins in the endoplasmic reticulum or (2) misrouting of correctly folded proteins.

Keywords:

  • Diabetes Insipidus;
  • Central Diabetes Insipidus;
  • Nephrogenic Diabetes Insipidus;
  • Vasopressin;
  • Oxytocin;
  • G protein-coupled Receptors;
  • Heterotrimeric G-proteins;
  • Aquaporins