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

Ghrelin secretion stimulated by β1-adrenergic receptors in cultured ghrelinoma cells and in fasted mice
Tong-Jin Zhaoa,1, Ichiro Sakatab,1, Robert Lin Lia, Guosheng Lianga, James A. Richardsonc, Michael S. Browna,2, Joseph L. Goldsteina,2, and Jeffrey M. Zigmanb,d,2
+ Author Affiliations

Departments of aMolecular Genetics,
bInternal Medicine (Divisions of Hypothalamic Research and Endocrinology and Metabolism),
cPathology, and
dPsychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390
Contributed by Michael S. Brown, July 27, 2010 (sent for review July 15, 2010)

↵1T.-J.Z. and I.S. contributed equally to this work.

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.

endocrine tumorsPG-1 cellsatenololoctanoateSV40-T antigen

Footnotes
2To whom correspondence may be addressed. E-mail: joe.goldstein@utsouthwestern.edu, mike.brown@utsouthwestern.edu, or jeffrey.zigman@utsouthwestern.edu. Author contributions: T.-J.Z., I.S., R.L.L., G.L., M.S.B., J.L.G., and J.M.Z. designed research; T.-J.Z., I.S., R.L.L., G.L., and J.A.R. performed research; T.-J.Z., I.S., R.L.L., G.L., M.S.B., J.L.G., and J.M.Z. analyzed data; and T.-J.Z., G.L., M.S.B., J.L.G., and J.M.Z. wrote the paper.

The authors declare no conflict of interest.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1011116107/-/DCSupplemental.
Ghrelin secretion stimulated by β1-adrenergic receptors in cultured ghrelinoma cells and in fasted mice — PNAS