Characterization of the zebrafish (Danio rerio) mineralocorticoid receptor

Mol Cell Endocrinol. 2011 Jan 30;332(1-2):58-66. doi: 10.1016/j.mce.2010.09.014. Epub 2010 Oct 12.

Abstract

Comparison between evolutionarily distant receptors can provide critical insights into both structure and function. Sequence comparison between the mineralocorticoid receptors (MR) of the zebrafish (zMR) and human (hMR) reveals a high degree of sequence conservation in the major functional domains. We isolated a zMR cDNA to contrast the transcriptional response to a range of ligands and to establish whether a teleost MR exhibits the amino/carboxyl-terminal interaction (N/C-interaction) previously reported for the hMR. Aldosterone, deoxycorticosterone (DOC) and cortisol induced zMR transcriptional activity with similar efficacy to that observed with the hMR. The hMR antagonist, spironolactone, acted as an agonist with the zMR. The zMR exhibited an N/C-interaction in response to aldosterone but, in contrast to the hMR, cortisol and DOC predominantly stimulated the interaction in the zMR. Conservation of the N/C-interaction between evolutionarily distant MR provides evidence of functional significance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldosterone / metabolism
  • Aldosterone / pharmacology
  • Amino Acid Sequence
  • Animals
  • Antihypertensive Agents / metabolism
  • Antihypertensive Agents / pharmacology
  • Cell Line
  • Desoxycorticosterone / metabolism
  • Desoxycorticosterone / pharmacology
  • Humans
  • Hydrocortisone / metabolism
  • Hydrocortisone / pharmacology
  • Mineralocorticoid Receptor Antagonists / metabolism
  • Mineralocorticoid Receptor Antagonists / pharmacology
  • Molecular Sequence Data
  • Nimodipine / metabolism
  • Nimodipine / pharmacology
  • Receptors, Mineralocorticoid / agonists
  • Receptors, Mineralocorticoid / genetics
  • Receptors, Mineralocorticoid / metabolism*
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Spironolactone / metabolism
  • Spironolactone / pharmacology
  • Transcriptional Activation / drug effects
  • Zebrafish / anatomy & histology
  • Zebrafish / genetics
  • Zebrafish / metabolism*

Substances

  • Antihypertensive Agents
  • Mineralocorticoid Receptor Antagonists
  • Receptors, Mineralocorticoid
  • Spironolactone
  • Desoxycorticosterone
  • Aldosterone
  • Nimodipine
  • Hydrocortisone