Cholinergic Regulation of Orexin/Hypocretin Neurons Through M3Muscarinic Receptor in Mice
The cholinergic system plays an important role in regulation of arousal and REM sleep. In the present study, we showed that a muscarinic receptor agonist, carbachol (CCh), activates almost 20% of orexin-producing neurons (orexin neurons), which play a critical role in maintenance of arousal. We also...
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doaj-556b775eb53a46abac09c4183b8c9e252020-11-25T02:20:48ZengElsevierJournal of Pharmacological Sciences1347-86132008-01-011063485491Cholinergic Regulation of Orexin/Hypocretin Neurons Through M3Muscarinic Receptor in MiceKousaku Ohno0Mari Hondo1Takeshi Sakurai2Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki 305-8575, JapanDepartment of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki 305-8575, JapanDepartment of Molecular Neuroscience and Integrative Physiology, Graduate School of Medical Science, Kanazawa University, 13-1 Takaramachi, Kanazawa-shi, Ishikawa 920-8640, Japan; Corresponding author. tsakurai@med.kanazawa-u.ac.jpThe cholinergic system plays an important role in regulation of arousal and REM sleep. In the present study, we showed that a muscarinic receptor agonist, carbachol (CCh), activates almost 20% of orexin-producing neurons (orexin neurons), which play a critical role in maintenance of arousal. We also found that a very small population of orexin neurons (1%) was inhibited by CCh. Muscarinic receptor antagonists inhibited the CCh-induced activation of orexin neurons in a dose-dependent manner. The M3-selective muscarinic receptor antagonist 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP) affected the response at a significantly lower concentration compared with the M1-selective muscarinic antagonist pirenzepine. IC50of 4-DAMP and pirenzepine was 0.30 ± 0.15 and 59.9 ± 18.6 nM, respectively. The CCh-induced inward current was attenuated by the nonselective cation channel blocker SKF96365. These results indicate that CCh activates 20% of orexin neurons through the M3muscarinic receptor and subsequent activation of nonselective cation channels. Keywords:: orexin, hypocretin, acetylcholine, nonselective cation channel, muscarinic receptorhttp://www.sciencedirect.com/science/article/pii/S1347861319340794 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kousaku Ohno Mari Hondo Takeshi Sakurai |
spellingShingle |
Kousaku Ohno Mari Hondo Takeshi Sakurai Cholinergic Regulation of Orexin/Hypocretin Neurons Through M3Muscarinic Receptor in Mice Journal of Pharmacological Sciences |
author_facet |
Kousaku Ohno Mari Hondo Takeshi Sakurai |
author_sort |
Kousaku Ohno |
title |
Cholinergic Regulation of Orexin/Hypocretin Neurons Through M3Muscarinic Receptor in Mice |
title_short |
Cholinergic Regulation of Orexin/Hypocretin Neurons Through M3Muscarinic Receptor in Mice |
title_full |
Cholinergic Regulation of Orexin/Hypocretin Neurons Through M3Muscarinic Receptor in Mice |
title_fullStr |
Cholinergic Regulation of Orexin/Hypocretin Neurons Through M3Muscarinic Receptor in Mice |
title_full_unstemmed |
Cholinergic Regulation of Orexin/Hypocretin Neurons Through M3Muscarinic Receptor in Mice |
title_sort |
cholinergic regulation of orexin/hypocretin neurons through m3muscarinic receptor in mice |
publisher |
Elsevier |
series |
Journal of Pharmacological Sciences |
issn |
1347-8613 |
publishDate |
2008-01-01 |
description |
The cholinergic system plays an important role in regulation of arousal and REM sleep. In the present study, we showed that a muscarinic receptor agonist, carbachol (CCh), activates almost 20% of orexin-producing neurons (orexin neurons), which play a critical role in maintenance of arousal. We also found that a very small population of orexin neurons (1%) was inhibited by CCh. Muscarinic receptor antagonists inhibited the CCh-induced activation of orexin neurons in a dose-dependent manner. The M3-selective muscarinic receptor antagonist 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP) affected the response at a significantly lower concentration compared with the M1-selective muscarinic antagonist pirenzepine. IC50of 4-DAMP and pirenzepine was 0.30 ± 0.15 and 59.9 ± 18.6 nM, respectively. The CCh-induced inward current was attenuated by the nonselective cation channel blocker SKF96365. These results indicate that CCh activates 20% of orexin neurons through the M3muscarinic receptor and subsequent activation of nonselective cation channels. Keywords:: orexin, hypocretin, acetylcholine, nonselective cation channel, muscarinic receptor |
url |
http://www.sciencedirect.com/science/article/pii/S1347861319340794 |
work_keys_str_mv |
AT kousakuohno cholinergicregulationoforexinhypocretinneuronsthroughm3muscarinicreceptorinmice AT marihondo cholinergicregulationoforexinhypocretinneuronsthroughm3muscarinicreceptorinmice AT takeshisakurai cholinergicregulationoforexinhypocretinneuronsthroughm3muscarinicreceptorinmice |
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