Journal article
Modulation of nicotinic receptor channels by adrenergic stimulation in rat pinealocytes
American Journal of Physiology: Cell Physiology, Vol.306(8), pp.C726-C735
04/01/2014
DOI: 10.1152/ajpcell.00354.2013
PMCID: PMC3989718
PMID: 24553185
Abstract
Melatonin secretion from the pineal gland is triggered by norepinephrine released from sympathetic terminals at night. In contrast, cholinergic and parasympathetic inputs, by activating nicotinic cholinergic receptors (nAChR), have been suggested to counterbalance the noradrenergic input. Here we investigated whether adrenergic signaling regulates nAChR channels in rat pinealocytes. Acetylcholine or the selective nicotinic receptor agonist 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) activated large nAChR currents in whole cell patch-clamp experiments. Norepinephrine (NE) reduced the nAChR currents, an effect partially mimicked by a beta-adrenergic receptor agonist, isoproterenol, and blocked by a beta-adrenergic receptor antagonist, propranolol. Increasing intracellular cAMP levels using membrane-permeable 8-bromoadenosine (8-Br)cAMP or 5,6-dichlorobenzimidazole riboside-3 ', 5 '-cyclic monophosphorothioate (cBIMPS) also reduced nAChR activity, mimicking the effects of NE and isoproterenol. Further, removal of ATP from the intracellular pipette solution blocked the reduction of nAChR currents, suggesting involvement of protein kinases. Indeed protein kinase A inhibitors, H-89 and Rp-cAMPS, blocked the modulation of nAChR by adrenergic stimulation. After the downmodulation by NE, nAChR channels mediated a smaller Ca2+ influx and less membrane depolarization from the resting potential. Together these results suggest that NE released from sympathetic terminals at night attenuates nicotinic cholinergic signaling.
Details
- Title: Subtitle
- Modulation of nicotinic receptor channels by adrenergic stimulation in rat pinealocytes
- Creators
- Jin-Young Yoon - University of WashingtonSeung-Ryoung Jung - University of WashingtonBertil Hille - University of WashingtonDuk-Su Koh - University of Washington
- Resource Type
- Journal article
- Publication Details
- American Journal of Physiology: Cell Physiology, Vol.306(8), pp.C726-C735
- Publisher
- Amer Physiological Soc
- DOI
- 10.1152/ajpcell.00354.2013
- PMID
- 24553185
- PMCID
- PMC3989718
- ISSN
- 0363-6143
- eISSN
- 1522-1563
- Number of pages
- 10
- Grant note
- R01NS008174 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) R01GM083913 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) DK-080840 / National Institute of Diabetes and Digestive and Kidney Diseases; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) NS-08174 / National Institute of Neurological Disorders and Stroke; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) GM-83913 / National Institute of General Medical Sciences; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) R01DK080840 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
- Language
- English
- Date published
- 04/01/2014
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984363264602771
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