Muscarinic M1 receptors stimulated by intracerebroventricular administration of McN-A-343 reduces the nerve injury-induced mechanical hypersensitivity via GABAB receptors rather than GABAA receptors in mice
Cholinergic neurons play an important role in the higher functions of the brain, such as the memory, cognition, and nociception. However, the exact mechanism behind how the stimulation of all the muscarinic M1 receptors in the entire brain results in the alleviation of partial sciatic nerve ligation...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-02-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319341751 |
| _version_ | 1828462887620837376 |
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| author | Keisuke Migita Akiko Nishimura Fumihiro Eto Kohei Koga Taichi Matsumoto Kazuki Terada Shuji Hara Kenji Honda |
| author_facet | Keisuke Migita Akiko Nishimura Fumihiro Eto Kohei Koga Taichi Matsumoto Kazuki Terada Shuji Hara Kenji Honda |
| author_sort | Keisuke Migita |
| collection | DOAJ |
| description | Cholinergic neurons play an important role in the higher functions of the brain, such as the memory, cognition, and nociception. However, the exact mechanism behind how the stimulation of all the muscarinic M1 receptors in the entire brain results in the alleviation of partial sciatic nerve ligation (PSNL)-induced mechanical hypersensitivity has not been investigated. Thus, we examined which subtype of GABA receptor was involved in the alleviation of PSNL-induce mechanical hypersensitivity produced by an intracerebroventricular administration of a muscarinic M1 receptor agonist, McN-A-343. Administering a GABAA receptor antagonist, bicuculline, resulted in no changes to the McN-A-343-induced anti-hypersensitivity in PSNL mice whereas a GABAB receptor antagonist, CGP35348, dose-dependently inhibited the anti-hypersensitivity. Furthermore, CGP35348 increased mechanical hypersensitivity in naïve mice, and the hypersensitivity was blocked by NMDA receptor antagonists, MK-801 and D-AP5. Additionally, muscarinic M1 receptors colocalized with GABAB1 receptors and an NMDA receptor subunit, GluN2A, in a large region of the brain. Consequently, these results suggest that the activation of muscarinic M1 receptors in the entire brain reduces nerve injury-induced mechanical hypersensitivity via the GABAB receptors, and the activation of the GABAB receptors regulates glutamatergic transmission via NMDA receptors. Keywords: Muscarinic M1 receptor, GABAB receptor, NMDA receptor, Intracerebroventricular administration, Partial sciatic nerve ligation model |
| first_indexed | 2024-12-11T02:44:01Z |
| format | Article |
| id | doaj.art-8fcf14684b8b4adda7c2721b6364cbdf |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-11T02:44:01Z |
| publishDate | 2020-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-8fcf14684b8b4adda7c2721b6364cbdf2022-12-22T01:23:29ZengElsevierJournal of Pharmacological Sciences1347-86132020-02-0114225059Muscarinic M1 receptors stimulated by intracerebroventricular administration of McN-A-343 reduces the nerve injury-induced mechanical hypersensitivity via GABAB receptors rather than GABAA receptors in miceKeisuke Migita0Akiko Nishimura1Fumihiro Eto2Kohei Koga3Taichi Matsumoto4Kazuki Terada5Shuji Hara6Kenji Honda7Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan; Corresponding author. Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jounan-ku, Fukuoka 814-0180, Japan. Fax: +81 92 863 0389.Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, JapanDepartment of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan; Department of Optical Imaging, Institute for Medical Photonics Research, Preeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine, Shizuoka 431-3192, JapanDepartment of Neurophysiology, Hyogo College of Medicine, Hyogo 663-8501, JapanDepartment of Drug Informatics, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, JapanLaboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, JapanDepartment of Drug Informatics, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, JapanDepartment of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan; Department of Neurophysiology, Hyogo College of Medicine, Hyogo 663-8501, Japan; Corresponding author. Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan. Fax: +81 92 863 0389.Cholinergic neurons play an important role in the higher functions of the brain, such as the memory, cognition, and nociception. However, the exact mechanism behind how the stimulation of all the muscarinic M1 receptors in the entire brain results in the alleviation of partial sciatic nerve ligation (PSNL)-induced mechanical hypersensitivity has not been investigated. Thus, we examined which subtype of GABA receptor was involved in the alleviation of PSNL-induce mechanical hypersensitivity produced by an intracerebroventricular administration of a muscarinic M1 receptor agonist, McN-A-343. Administering a GABAA receptor antagonist, bicuculline, resulted in no changes to the McN-A-343-induced anti-hypersensitivity in PSNL mice whereas a GABAB receptor antagonist, CGP35348, dose-dependently inhibited the anti-hypersensitivity. Furthermore, CGP35348 increased mechanical hypersensitivity in naïve mice, and the hypersensitivity was blocked by NMDA receptor antagonists, MK-801 and D-AP5. Additionally, muscarinic M1 receptors colocalized with GABAB1 receptors and an NMDA receptor subunit, GluN2A, in a large region of the brain. Consequently, these results suggest that the activation of muscarinic M1 receptors in the entire brain reduces nerve injury-induced mechanical hypersensitivity via the GABAB receptors, and the activation of the GABAB receptors regulates glutamatergic transmission via NMDA receptors. Keywords: Muscarinic M1 receptor, GABAB receptor, NMDA receptor, Intracerebroventricular administration, Partial sciatic nerve ligation modelhttp://www.sciencedirect.com/science/article/pii/S1347861319341751 |
| spellingShingle | Keisuke Migita Akiko Nishimura Fumihiro Eto Kohei Koga Taichi Matsumoto Kazuki Terada Shuji Hara Kenji Honda Muscarinic M1 receptors stimulated by intracerebroventricular administration of McN-A-343 reduces the nerve injury-induced mechanical hypersensitivity via GABAB receptors rather than GABAA receptors in mice Journal of Pharmacological Sciences |
| title | Muscarinic M1 receptors stimulated by intracerebroventricular administration of McN-A-343 reduces the nerve injury-induced mechanical hypersensitivity via GABAB receptors rather than GABAA receptors in mice |
| title_full | Muscarinic M1 receptors stimulated by intracerebroventricular administration of McN-A-343 reduces the nerve injury-induced mechanical hypersensitivity via GABAB receptors rather than GABAA receptors in mice |
| title_fullStr | Muscarinic M1 receptors stimulated by intracerebroventricular administration of McN-A-343 reduces the nerve injury-induced mechanical hypersensitivity via GABAB receptors rather than GABAA receptors in mice |
| title_full_unstemmed | Muscarinic M1 receptors stimulated by intracerebroventricular administration of McN-A-343 reduces the nerve injury-induced mechanical hypersensitivity via GABAB receptors rather than GABAA receptors in mice |
| title_short | Muscarinic M1 receptors stimulated by intracerebroventricular administration of McN-A-343 reduces the nerve injury-induced mechanical hypersensitivity via GABAB receptors rather than GABAA receptors in mice |
| title_sort | muscarinic m1 receptors stimulated by intracerebroventricular administration of mcn a 343 reduces the nerve injury induced mechanical hypersensitivity via gabab receptors rather than gabaa receptors in mice |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319341751 |
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