title: Inhibitory Effect of Endomorphin-2 Binding to the μ-Opioid Receptor in the Rat Pre-Bötzinger Complex on the Breathing Activity.
abstract: Opiates are commonly used analgesics that often cause clinical respiratory depression. However, their underlying mechanisms remain unclear. Endomorphin-2 (EM2) is a novel, endogenous tetrapeptide opioid with very high affinity and selectivity for the μ-opioid receptor (MOR). The pre-Bötzinger complex (pre-BötC) is considered the center of respiratory rhythm generation, and the synaptic connections in this region are essential for respiratory rhythm. The present study identified EM2-like immunoreactive (LI) axonal terminals in the pre-BötC of adult rats. Some EM2-LI axonal terminals made principally symmetric synapses with neurokinin 1 receptor (NK1R)-LI or MOR-LI neuronal dendritic processes in the pre-BötC. Unilateral microinjection of EM2 into the pre-BötC decreased breathing frequency and amplitude. A prior microinjection of the selective MOR antagonist β-funaltrexamine (β-FNA) into the pre-BötC prevented the effects of EM2. The present results suggest that EM2-LI axonal terminals modulate NK1R-expressing neurons in the pre-BötC and that EM2 plays a role in respiratory depression through MORs in the pre-BötC.
authors.affiliation: Department of Anatomy and Histology and Embryology and K. K. Leung Brain Research Centre, The Fourth Military Medical University, No. 169, West Changle Road, Xi'an, 710032, People's Republic of China.|Department of Spinal Cord Injury and Rehabilitation, The General Hospital of Jinan Military Command, Jinan, 250031, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Anatomy and Histology and Embryology and K. K. Leung Brain Research Centre, The Fourth Military Medical University, No. 169, West Changle Road, Xi'an, 710032, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Spinal Cord Injury and Rehabilitation, The General Hospital of Jinan Military Command, Jinan, 250031, China.
authors.forename: Ting-Bao
authors.initials: TB
authors.lastname: Zhao
authors.affiliation: Department of Anatomy and Histology and Embryology and K. K. Leung Brain Research Centre, The Fourth Military Medical University, No. 169, West Changle Road, Xi'an, 710032, People's Republic of China.
authors.forename: Ya-Cheng
authors.initials: YC
authors.lastname: Lu
authors.affiliation: Department of Anatomy and Histology and Embryology and K. K. Leung Brain Research Centre, The Fourth Military Medical University, No. 169, West Changle Road, Xi'an, 710032, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Anatomy and Histology and Embryology and K. K. Leung Brain Research Centre, The Fourth Military Medical University, No. 169, West Changle Road, Xi'an, 710032, People's Republic of China. jinlian@fmmu.edu.cn.
authors.forename: Jin-Lian
authors.initials: JL
authors.lastname: Li
authors.affiliation: Department of Anatomy and Histology and Embryology and K. K. Leung Brain Research Centre, The Fourth Military Medical University, No. 169, West Changle Road, Xi'an, 710032, People's Republic of China. donganat@fmmu.edu.cn.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Dong
authors.affiliation: Department of Anatomy and Histology and Embryology and K. K. Leung Brain Research Centre, The Fourth Military Medical University, No. 169, West Changle Road, Xi'an, 710032, People's Republic of China. deptanat@fmmu.edu.cn.|Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China. deptanat@fmmu.edu.cn.
authors.forename: Yun-Qing
authors.initials: YQ
authors.lastname: Li
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*
chemical_list: D009292:Narcotic Antagonists; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105294:endomorphin 2; D009271:Naltrexone; C024524:beta-funaltrexamine
keywords: Electron microscopy; Endomorphin-2; Neurokinin 1 receptor; Pre-Bötzinger complex; Rat; Respiratory depression; μ-opioid receptor