The pineal gland is an endocrine organ that is part of our circadian clock system in the brain. Throughout the night, noradrenaline released locally by the sympathetic nervous system stimulates the pineal to broadcast the night hormone, melatonin, to all of the body. We will study the early second-messenger signaling within isolated pinealocytes in response to applied norepinephrine, the longer term availability of adrenergic receptors during prolonged exposure to norepinephrine, and, in pineal slices and whole pineal glands, the modulatory actions of classical neurotransmitters on pinealocyte activity. We will determine the G-protein coupling of melatonin receptors expressed in various expression systems. Finally we will test the hypothesis that N-acetyl serotonin is a candidate for another night hormone in addition to melatonin. Cells will be dissociated from rat pineal glands, placed in cell culture, treated with norepinephrine to mimic night, and studied under the microscope with techniques such as whole-cell gigaseal electrophysiological recording, live-cell photometry of calcium-sensitive dyes and of indicators for second messengers, and HPLC-mass spectroscopy of the three indoleamine hormones. Solvent extracts of whole pineal glands will be analyzed by HPLC-mass spectroscopy for the phosphoinositides and other phospholipids of their membranes. 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 and productivity due to jet lag and shift work.

Public Health Relevance

We will study regulation by neurotransmitters of cells of the pineal gland as they secrete melatonin, the hormone of night. And we will study the response of other cells in the body to secreted melatonin. Understanding the rhythmic actions of the pineal will make an important contribution towards treating sleep disorders, seasonal affective responses to short days, and loss of attention and productivity due to jet lag and shift work.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM083913-41A1
Application #
9306424
Study Section
Neurotransporters, Receptors, and Calcium Signaling Study Section (NTRC)
Program Officer
Nie, Zhongzhen
Project Start
1977-09-01
Project End
2021-03-31
Budget Start
2017-04-01
Budget End
2018-03-31
Support Year
41
Fiscal Year
2017
Total Cost
$378,760
Indirect Cost
$134,201
Name
University of Washington
Department
Physiology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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

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