Polymorphism and signalling of melatonin receptors

L Brydon, L Petit, P de Coppet, Perry Barrett, Peter John Morgan, A D Strosberg, R Jockers

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Melatonin receptors belong to the superfamily of G protein-coupled receptors. Cloning of Melic receptors expressed in Xenopus skin revealed the existence of a polymorphism for these receptors. Heterologous expression of the two allelic isoforms, called Mel1c(alpha) and Mel1c(beta), indicated functional differences in their signalling properties. Both isoforms are coupled to the cAMP and cGMP pathways. However, the alpha isoform is preferentially coupled to the cAMP pathway, whereas the beta isoform couples preferentially to the cGMP pathway. Coupling differences may be explained by the fact that five of the six amino acid substitutions between the two isoforms are localized within intracellular receptor regions potentially involved in G protein coupling. Allelic isoforms were also observed for Mel1a receptors expressed in ovine pars tuberalis, suggesting that polymorphism is a general feature of the melatonin receptor family. We also evaluated the potential of the two human melatonin receptor subtypes, Mel1a and Mel1b, to modulate the cGMP pathway. Melatonin inhibited intracellular cGMP levels in a dose-dependent manner in HEK293 cells transfected with the human Mel1b receptor. This was not the case for HEK293 cells transfected with the human Mel1a receptor. In conclusion, our results indicate that the expression of receptor subtypes and isoforms may permit differential signalling between melatonin receptors. (C) Inra/Elsevier, Paris.

Original languageEnglish
Pages (from-to)315-324
Number of pages10
JournalReproduction, Nutrition, Development
Volume39
Issue number3
Publication statusPublished - May 1999

Keywords

  • melatonin receptor
  • polymorphism
  • signalling
  • suprachiasmatic circadian clock
  • guanylyl cyclase
  • nitric-oxide
  • G-proteins
  • cloning
  • transduction
  • pharmacology
  • subtypes

Cite this

Brydon, L., Petit, L., de Coppet, P., Barrett, P., Morgan, P. J., Strosberg, A. D., & Jockers, R. (1999). Polymorphism and signalling of melatonin receptors. Reproduction, Nutrition, Development, 39(3), 315-324.

Polymorphism and signalling of melatonin receptors. / Brydon, L ; Petit, L ; de Coppet, P ; Barrett, Perry; Morgan, Peter John; Strosberg, A D ; Jockers, R .

In: Reproduction, Nutrition, Development, Vol. 39, No. 3, 05.1999, p. 315-324.

Research output: Contribution to journalArticle

Brydon, L, Petit, L, de Coppet, P, Barrett, P, Morgan, PJ, Strosberg, AD & Jockers, R 1999, 'Polymorphism and signalling of melatonin receptors', Reproduction, Nutrition, Development, vol. 39, no. 3, pp. 315-324.
Brydon L, Petit L, de Coppet P, Barrett P, Morgan PJ, Strosberg AD et al. Polymorphism and signalling of melatonin receptors. Reproduction, Nutrition, Development. 1999 May;39(3):315-324.
Brydon, L ; Petit, L ; de Coppet, P ; Barrett, Perry ; Morgan, Peter John ; Strosberg, A D ; Jockers, R . / Polymorphism and signalling of melatonin receptors. In: Reproduction, Nutrition, Development. 1999 ; Vol. 39, No. 3. pp. 315-324.
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AB - Melatonin receptors belong to the superfamily of G protein-coupled receptors. Cloning of Melic receptors expressed in Xenopus skin revealed the existence of a polymorphism for these receptors. Heterologous expression of the two allelic isoforms, called Mel1c(alpha) and Mel1c(beta), indicated functional differences in their signalling properties. Both isoforms are coupled to the cAMP and cGMP pathways. However, the alpha isoform is preferentially coupled to the cAMP pathway, whereas the beta isoform couples preferentially to the cGMP pathway. Coupling differences may be explained by the fact that five of the six amino acid substitutions between the two isoforms are localized within intracellular receptor regions potentially involved in G protein coupling. Allelic isoforms were also observed for Mel1a receptors expressed in ovine pars tuberalis, suggesting that polymorphism is a general feature of the melatonin receptor family. We also evaluated the potential of the two human melatonin receptor subtypes, Mel1a and Mel1b, to modulate the cGMP pathway. Melatonin inhibited intracellular cGMP levels in a dose-dependent manner in HEK293 cells transfected with the human Mel1b receptor. This was not the case for HEK293 cells transfected with the human Mel1a receptor. In conclusion, our results indicate that the expression of receptor subtypes and isoforms may permit differential signalling between melatonin receptors. (C) Inra/Elsevier, Paris.

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