Molecular pharmacology of the ovine melatonin receptor: comparison with recombinant human MT1 and MT2 receptors

F Mailliet, V Audinot, B Malpaux, A Bonnaud, P Delagrange, M Migaud, Perry Barrett, M C Viaud-Massuard, D Lesieur, F Lefoulon, P Renard, J A Boutin

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Abstract

The variations of the pharmacological properties of melatonin receptors between different mammalian species in transfected cell lines have been poorly investigated. In the present study, melatonin analogues have been used to characterize the pharmacology of the recombinant ovine melatonin receptor (oMT(1)) expressed in CHO cell lines and the native oMT(1) from thepars tuberalis (PT). Studies with selective ligands on native and transfected oMT(1) showed similar properties for binding affinities [r(2)(PT/CHO) = 0.85]. The affinities and the functional activities of these ligands were compared with the human receptors (hMT(1) or hMT(2)) expressed in CHO cells as well. The oMT(1) and hMT(1) receptors had similar pharmacological profiles (r(2) = 0.82). Nevertheless, some of the selective compounds at the human receptor presented a reduced affinity at the ovine receptor. Furthermore, some compounds showed marked different functional activities at oMT(1) vs. hMT(1) receptors. Our findings demonstrated differences in the pharmacological properties of melatonin receptors in ovine and human species. (C) 2003 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)667-677
Number of pages11
JournalBiochemical Pharmacology
Volume67
Issue number4
Early online date4 Dec 2003
DOIs
Publication statusPublished - 15 Feb 2004

Keywords

  • melatonin
  • recombinant human melatonin receptors
  • recombinant ovine melatonin receptor
  • molecular pharmacology
  • Pars tuberalis
  • CHO cells
  • sheep pars tuberalis
  • amidic derivatives
  • selective ligands
  • human MEL(1A)
  • binding
  • retina
  • melanophores
  • antagonist
  • subtypes
  • cloning

Cite this

Mailliet, F., Audinot, V., Malpaux, B., Bonnaud, A., Delagrange, P., Migaud, M., Barrett, P., Viaud-Massuard, M. C., Lesieur, D., Lefoulon, F., Renard, P., & Boutin, J. A. (2004). Molecular pharmacology of the ovine melatonin receptor: comparison with recombinant human MT1 and MT2 receptors. Biochemical Pharmacology, 67(4), 667-677. https://doi.org/10.1016/j.bcp.2003.09.037