title: α7-cholinergic receptor mediates vagal induction of splenic norepinephrine.
abstract: Classically, sympathetic and parasympathetic systems act in opposition to maintain the physiological homeostasis. In this article, we report that both systems work together to restrain systemic inflammation in life-threatening conditions such as sepsis. This study indicates that vagus nerve and cholinergic agonists activate the sympathetic noradrenergic splenic nerve to control systemic inflammation. Unlike adrenalectomy, splenectomy and splenic neurectomy prevent the anti-inflammatory potential of both the vagus nerve and cholinergic agonists, and abrogate their potential to induce splenic and plasma norepinephrine. Splenic nerve stimulation mimics vagal and cholinergic induction of norepinephrine and re-establishes neuromodulation in α7 nicotinic acetylcholine receptor (α7nAChR)-deficient animals. Thus, vagus nerve and cholinergic agonists inhibit systemic inflammation by activating the noradrenergic splenic nerve via the α7nAChR nicotinic receptors. α7nAChR represents a unique molecular link between the parasympathetic and sympathetic system to control inflammation.
authors.affiliation: Laboratory of Anti-inflammatory Signaling and Surgical Immunology, Department of Surgery, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Gergely
authors.initials: G
authors.lastname: Vida
authors.forename: Geber
authors.initials: G
authors.lastname: Peña
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Deitch
authors.forename: Luis
authors.initials: L
authors.lastname: Ulloa
mesh_terms: D000818:Animals; D018679:Cholinergic Agonists / Q000494:pharmacology; D004525:Efferent Pathways / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009638:Norepinephrine / Q000096:biosynthesis* / Q000097:blood; D010275:Parasympathetic Nervous System / Q000276:immunology / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000276:immunology* / Q000294:innervation / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000276:immunology / Q000378:metabolism; D055536:Vagus Nerve Stimulation / Q000379:methods*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D018679:Cholinergic Agonists; C579166:Chrna7 protein, mouse; C579165:Chrna7 protein, rat; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009638:Norepinephrine