The human MT1 melatonin receptor stimulates cAMP production in the human neuroblastoma cell line SH-SY5Y cells via a calcium-calmodulin signal transduction pathway

C Schuster, Lynda Williams, Amanda Morris, Peter John Morgan, Perry Barrett

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Melatonin regulates circadian and seasonal physiology via melatonin receptors expressed in the brain. However, little is known about the signal transduction mechanisms that mediate the action of melatonin in neuronal cells. To begin to address this issue, we expressed the human MT1, receptor in the human neuroblastoma SH-SY5Y cell line. In this cell line, melatonin acutely stimulated cAMP synthesis through a calcium-calmodulin dependent pathway. This stimulatory effect was independent of an interaction with G(i) or G(s) G proteins and dependent upon internal calcium stores. Melatonin also potentiated forskolin-activated cAMP synthesis. Differentiation of the neuroblastoma cells with retinoic acid to the neuronal phenotype did not alter, the ability of melatonin to acutely stimulate cAMP. These data may be relevant to the neuronal action of melatonin and highlight the importance of the cellular context of expression of melatonin and other G protein-coupled receptors.

Original languageEnglish
Pages (from-to)170-178
Number of pages9
JournalJournal of Neuroendocrinology
Volume17
Issue number3
DOIs
Publication statusPublished - Mar 2005

Keywords

  • cell signalling
  • circadian
  • suprachiasmatic nucleus
  • pars tuberalis
  • ovine pars tuberalis
  • G-protein alpha
  • adenylate-cyclase
  • cyclic-amp
  • MT(1) melatonin
  • gene-expression
  • ligand-binding
  • cholera-toxin
  • humna MEL1A

Cite this

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title = "The human MT1 melatonin receptor stimulates cAMP production in the human neuroblastoma cell line SH-SY5Y cells via a calcium-calmodulin signal transduction pathway",
abstract = "Melatonin regulates circadian and seasonal physiology via melatonin receptors expressed in the brain. However, little is known about the signal transduction mechanisms that mediate the action of melatonin in neuronal cells. To begin to address this issue, we expressed the human MT1, receptor in the human neuroblastoma SH-SY5Y cell line. In this cell line, melatonin acutely stimulated cAMP synthesis through a calcium-calmodulin dependent pathway. This stimulatory effect was independent of an interaction with G(i) or G(s) G proteins and dependent upon internal calcium stores. Melatonin also potentiated forskolin-activated cAMP synthesis. Differentiation of the neuroblastoma cells with retinoic acid to the neuronal phenotype did not alter, the ability of melatonin to acutely stimulate cAMP. These data may be relevant to the neuronal action of melatonin and highlight the importance of the cellular context of expression of melatonin and other G protein-coupled receptors.",
keywords = "cell signalling, circadian, suprachiasmatic nucleus, pars tuberalis, ovine pars tuberalis, G-protein alpha, adenylate-cyclase, cyclic-amp, MT(1) melatonin, gene-expression, ligand-binding, cholera-toxin, humna MEL1A",
author = "C Schuster and Lynda Williams and Amanda Morris and Morgan, {Peter John} and Perry Barrett",
year = "2005",
month = "3",
doi = "10.1111/j.1365-2826.2005.01288.x",
language = "English",
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journal = "Journal of Neuroendocrinology",
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TY - JOUR

T1 - The human MT1 melatonin receptor stimulates cAMP production in the human neuroblastoma cell line SH-SY5Y cells via a calcium-calmodulin signal transduction pathway

AU - Schuster, C

AU - Williams, Lynda

AU - Morris, Amanda

AU - Morgan, Peter John

AU - Barrett, Perry

PY - 2005/3

Y1 - 2005/3

N2 - Melatonin regulates circadian and seasonal physiology via melatonin receptors expressed in the brain. However, little is known about the signal transduction mechanisms that mediate the action of melatonin in neuronal cells. To begin to address this issue, we expressed the human MT1, receptor in the human neuroblastoma SH-SY5Y cell line. In this cell line, melatonin acutely stimulated cAMP synthesis through a calcium-calmodulin dependent pathway. This stimulatory effect was independent of an interaction with G(i) or G(s) G proteins and dependent upon internal calcium stores. Melatonin also potentiated forskolin-activated cAMP synthesis. Differentiation of the neuroblastoma cells with retinoic acid to the neuronal phenotype did not alter, the ability of melatonin to acutely stimulate cAMP. These data may be relevant to the neuronal action of melatonin and highlight the importance of the cellular context of expression of melatonin and other G protein-coupled receptors.

AB - Melatonin regulates circadian and seasonal physiology via melatonin receptors expressed in the brain. However, little is known about the signal transduction mechanisms that mediate the action of melatonin in neuronal cells. To begin to address this issue, we expressed the human MT1, receptor in the human neuroblastoma SH-SY5Y cell line. In this cell line, melatonin acutely stimulated cAMP synthesis through a calcium-calmodulin dependent pathway. This stimulatory effect was independent of an interaction with G(i) or G(s) G proteins and dependent upon internal calcium stores. Melatonin also potentiated forskolin-activated cAMP synthesis. Differentiation of the neuroblastoma cells with retinoic acid to the neuronal phenotype did not alter, the ability of melatonin to acutely stimulate cAMP. These data may be relevant to the neuronal action of melatonin and highlight the importance of the cellular context of expression of melatonin and other G protein-coupled receptors.

KW - cell signalling

KW - circadian

KW - suprachiasmatic nucleus

KW - pars tuberalis

KW - ovine pars tuberalis

KW - G-protein alpha

KW - adenylate-cyclase

KW - cyclic-amp

KW - MT(1) melatonin

KW - gene-expression

KW - ligand-binding

KW - cholera-toxin

KW - humna MEL1A

U2 - 10.1111/j.1365-2826.2005.01288.x

DO - 10.1111/j.1365-2826.2005.01288.x

M3 - Article

VL - 17

SP - 170

EP - 178

JO - Journal of Neuroendocrinology

JF - Journal of Neuroendocrinology

SN - 0953-8194

IS - 3

ER -