Ghrelin secretion stimulated by β1-adrenergic receptors in cultured ghrelinoma cells and in fasted mice

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Abstract

Ghrelin, an octanoylated peptide hormone produced in the stomach, rises dramatically in mouse plasma during chronic severe calorie deprivation, an event that is essential to maintain life. The mechanism for this increase is not understood. Here, we study the control of ghrelin secretion in tissue culture cells derived from mice bearing ghrelinomas induced by a tissue-specific SV40 T-antigen transgene. We found that the ghrelin-secreting cells express high levels of mRNA encoding β1-adrenergic receptors. Addition of norepinephrine or epinephrine to the culture medium stimulated ghrelin secretion, and this effect was blocked by atenolol, a selective β1-adrenergic antagonist. When WT mice were treated with reserpine to deplete adrenergic neurotransmitters from sympathetic neurons, the fasting-induced increase in plasma ghrelin was blocked. Inhibition was also seen following atenolol administration. We conclude that ghrelin secretion during fasting is induced by adrenergic agents released by sympathetic neurons and acting directly on β1 receptors on the ghrelin-secreting cells of the stomach.

Original languageEnglish (US)
Pages (from-to)15868-15873
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number36
DOIs
StatePublished - Sep 7 2010

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Ghrelin
Adrenergic Receptors
Cultured Cells
Atenolol
Adrenergic Agents
Fasting
Stomach
Ghrelin Receptor
Polyomavirus Transforming Antigens
Neurons
Adrenergic Antagonists
Peptide Hormones
Reserpine
Transgenes
Epinephrine
Neurotransmitter Agents
Culture Media
Norepinephrine
Cell Culture Techniques
Messenger RNA

Keywords

  • Atenolol
  • Endocrine tumors
  • Octanoate
  • PG-1 cells
  • SV40-T antigen

ASJC Scopus subject areas

  • General

Cite this

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title = "Ghrelin secretion stimulated by β1-adrenergic receptors in cultured ghrelinoma cells and in fasted mice",
abstract = "Ghrelin, an octanoylated peptide hormone produced in the stomach, rises dramatically in mouse plasma during chronic severe calorie deprivation, an event that is essential to maintain life. The mechanism for this increase is not understood. Here, we study the control of ghrelin secretion in tissue culture cells derived from mice bearing ghrelinomas induced by a tissue-specific SV40 T-antigen transgene. We found that the ghrelin-secreting cells express high levels of mRNA encoding β1-adrenergic receptors. Addition of norepinephrine or epinephrine to the culture medium stimulated ghrelin secretion, and this effect was blocked by atenolol, a selective β1-adrenergic antagonist. When WT mice were treated with reserpine to deplete adrenergic neurotransmitters from sympathetic neurons, the fasting-induced increase in plasma ghrelin was blocked. Inhibition was also seen following atenolol administration. We conclude that ghrelin secretion during fasting is induced by adrenergic agents released by sympathetic neurons and acting directly on β1 receptors on the ghrelin-secreting cells of the stomach.",
keywords = "Atenolol, Endocrine tumors, Octanoate, PG-1 cells, SV40-T antigen",
author = "Zhao, {Tong Jin} and Ichiro Sakata and Li, {Robert Lin} and Guosheng Liang and Richardson, {James A.} and Brown, {Michael S.} and Goldstein, {Joseph L.} and Zigman, {Jeffrey M.}",
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AU - Zhao, Tong Jin

AU - Sakata, Ichiro

AU - Li, Robert Lin

AU - Liang, Guosheng

AU - Richardson, James A.

AU - Brown, Michael S.

AU - Goldstein, Joseph L.

AU - Zigman, Jeffrey M.

PY - 2010/9/7

Y1 - 2010/9/7

N2 - Ghrelin, an octanoylated peptide hormone produced in the stomach, rises dramatically in mouse plasma during chronic severe calorie deprivation, an event that is essential to maintain life. The mechanism for this increase is not understood. Here, we study the control of ghrelin secretion in tissue culture cells derived from mice bearing ghrelinomas induced by a tissue-specific SV40 T-antigen transgene. We found that the ghrelin-secreting cells express high levels of mRNA encoding β1-adrenergic receptors. Addition of norepinephrine or epinephrine to the culture medium stimulated ghrelin secretion, and this effect was blocked by atenolol, a selective β1-adrenergic antagonist. When WT mice were treated with reserpine to deplete adrenergic neurotransmitters from sympathetic neurons, the fasting-induced increase in plasma ghrelin was blocked. Inhibition was also seen following atenolol administration. We conclude that ghrelin secretion during fasting is induced by adrenergic agents released by sympathetic neurons and acting directly on β1 receptors on the ghrelin-secreting cells of the stomach.

AB - Ghrelin, an octanoylated peptide hormone produced in the stomach, rises dramatically in mouse plasma during chronic severe calorie deprivation, an event that is essential to maintain life. The mechanism for this increase is not understood. Here, we study the control of ghrelin secretion in tissue culture cells derived from mice bearing ghrelinomas induced by a tissue-specific SV40 T-antigen transgene. We found that the ghrelin-secreting cells express high levels of mRNA encoding β1-adrenergic receptors. Addition of norepinephrine or epinephrine to the culture medium stimulated ghrelin secretion, and this effect was blocked by atenolol, a selective β1-adrenergic antagonist. When WT mice were treated with reserpine to deplete adrenergic neurotransmitters from sympathetic neurons, the fasting-induced increase in plasma ghrelin was blocked. Inhibition was also seen following atenolol administration. We conclude that ghrelin secretion during fasting is induced by adrenergic agents released by sympathetic neurons and acting directly on β1 receptors on the ghrelin-secreting cells of the stomach.

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