Molecular and pharmacological characterization of the melanocortin type 1 receptor in the sea bass

  • Sánchez E
  • Rubio V
  • Cerdá-Reverter J
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Melanocortin 1 receptor (MC1R) plays a key role in the physiology of the vertebrate pigment system. Point mutations producing hyperactive or inactive receptors result in darkening or paling effects, respectively. We report the molecular and pharmacological characterization, as well as the tissue expression pattern, of the sea bass Mc1r. Similar to other MC1Rs, the sea bass gene is highly polymorphic and nine DNA polymorphisms, seven of them involving an amino acid substitution, were detected. SbMc1r is mainly expressed in the testis, fat and liver with moderate levels in the ventral and dorsal skin. The sea bass receptor was activated by all the melanocortins tested, with ACTH showing the lowest efficiency. The acetylation level of the MSH isoforms seems to be critical for the effectively of the agonist. Agouti-related protein (AGRP) drastically inhibited the basal activity of the receptor in vitro, as an inverse agonist does, but only in the presence of phosphodiesterase inhibitors. This observation suggests that sbMc1r is constitutively activated and inversely regulated by AGRP, which is expressed in the skin of different fish species. © 2009 Elsevier Inc. All rights reserved.

Author-supplied keywords

  • Agouti-related protein (AGRP)
  • Constitutive activity
  • Fish
  • IBMX
  • Inverse agonism
  • Melanocortin receptor 1 (MC1R)
  • Phosphodiesterase inhibitor

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