The pineal gland is an endocrine organ in the brain that is primarily regulated by noradrenaline released by the sympathetic nervous system. It is the part of our circadian clock system that broadcasts the night hormone, melatonin, to all of the body. The night state of pinealocytes is accompanied by extensive changes in gene expression relative to the day state. Many expressed genes are those expressed by a sister lineage, photoreceptors, except that mammalian pinealocytes are not photosensitive. Our overall hypothesis is that pinealocytes switch between two very different electrophysiological excitability states that contribute to regulated secretion of melatonin and to entrainment and maintenance of circadian rhythms. Using biophysical techniques, the night and day states of cultured rat pinealocytes will be contrasted in terms of their ion channel complement, calcium signal dynamics, receptor activation, second messenger levels, and secretory mechanisms. The state changes will be achieved by preincubating cultured primary cells in appropriate neurotransmitters. Cells will be dissociated from rat pineal glands, placed in cell culture, treate with norepinephrine to mimic night, and studied under the microscope with techniques such as whole-cell gigaseal recording, photometry of calcium-sensitive dyes, amperometry and HPLC of neurotransmitters, and use of various live-cell indicators for second messengers. Night pinealocytes are hypothesized to have electrical excitability related to that of photoreceptors, and day pinealocytes are hypothesized to be relatively quiescent. The hypothesis that serotonin is secreted from pinealocytes by quantal exocytosis whereas melatonin and N-acetyl serotonin are secreted by hydrophobic diffusion will also be tested. Understanding the rhythmic secretory mechanisms of the pineal will make an important contribution towards treating sleep disorders, seasonal affective responses to short days, and loss of attention due to jet lag and shift work.

Public Health Relevance

Cells of the pineal gland in the brain secrete melatonin, the hormone of night. We will study how their excitability differs in the secreting night state from th quiescent day state. Under- standing the rhythmic secretory mechanisms of the pineal will make an important contribution towards treating sleep disorders, seasonal affective responses to short days, and loss of attention due to jet lag and shift work.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Neurotransporters, Receptors, and Calcium Signaling Study Section (NTRC)
Program Officer
Nie, Zhongzhen
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Washington
Schools of Medicine
United States
Zip Code
Jung, Seung-Ryoung; Deng, Yi; Kushmerick, Christopher et al. (2018) Minimizing ATP depletion by oxygen scavengers for single-molecule fluorescence imaging in live cells. Proc Natl Acad Sci U S A 115:E5706-E5715
Jung, Seung-Ryoung; Seo, Jong Bae; Deng, Yi et al. (2016) Contributions of protein kinases and ?-arrestin to termination of protease-activated receptor 2 signaling. J Gen Physiol 147:255-71
Yu, Haijie; Dickson, Eamonn J; Jung, Seung-Ryoung et al. (2016) High membrane permeability for melatonin. J Gen Physiol 147:63-76
Yu, Haijie; Benitez, Sergio G; Jung, Seung-Ryoung et al. (2016) GABAergic signaling in the rat pineal gland. J Pineal Res 61:69-81
Yu, Haijie; Seo, Jong Bae; Jung, Seung-Ryoung et al. (2015) Noradrenaline upregulates T-type calcium channels in rat pinealocytes. J Physiol 593:887-904
Seo, Jong Bae; Moody, Mark; Koh, Duk-Su (2014) Epithelial monolayer culture system for real-time single-cell analyses. Physiol Rep 2:e12002
Liang, Kuo; Du, Wen; Lu, Jingze et al. (2014) Alterations of the Ca²? signaling pathway in pancreatic beta-cells isolated from db/db mice. Protein Cell 5:783-94
Yoon, Jin-Young; Jung, Seung-Ryoung; Hille, Bertil et al. (2014) Modulation of nicotinic receptor channels by adrenergic stimulation in rat pinealocytes. Am J Physiol Cell Physiol 306:C726-35
Koh, Duk-Su; Moody, Mark; Jo, Junghyo (2013) Collection of islets of Langerhans using an equilibrium method. Biotechniques 55:34-7
Dickson, Eamonn J; Falkenburger, Björn H; Hille, Bertil (2013) Quantitative properties and receptor reserve of the IP(3) and calcium branch of G(q)-coupled receptor signaling. J Gen Physiol 141:521-35

Showing the most recent 10 out of 24 publications