title: The alpha3 subtype of the nicotinic acetylcholine receptor is expressed in airway-related neurons of the nucleus tractus solitarius, but is not essential for reflex bronchoconstriction in ferrets.
abstract: To assess the role of nicotinic acetylcholine receptors (nACh-R) in the transmission of afferent constricting inputs from bronchopulmonary receptors to the nucleus tractus solitarius (nTS) and in the mediation of reflex airway constriction, we performed a combined immunohistological and functional study. In ferrets, the expression of nAch-R on the nTS neurons activated by histamine stimulation of airway sensory receptors was studied using laser scanning confocal microscopy to co-immunolocalize c-fos encoded protein (cFos) and nACh-R alpha3 subunit. We observed that activation of airway sensory receptors by inhalation of aerosolized histamine, induced cFos expression in a subset of nTS neurons that also expressed the nAch-R alpha3 subtype. Furthermore, activation of nACh-R within the commissural subnucleus by nicotine, increased cholinergic outflow to the airways. These effects were diminished by prior administration of hexamethonium (nACh-R blocker) within the commissural subnucleus of the nTS. However, hexamethonium had no significant effects on airway reflex constrictions induced by lung deflation. These findings indicate that nACh-R are expressed by the nTS neurons receiving inputs from airway sensory receptors, activation of which by nicotine increases cholinergic outflow to the airways, but the nACh-R pathways are not required for reflex bronchoconstriction.
authors.affiliation: Department of Anatomy, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: D G
authors.initials: DG
authors.lastname: Ferguson
authors.forename: M A
authors.initials: MA
authors.lastname: Haxhiu
authors.forename: A J
authors.initials: AJ
authors.lastname: To
authors.forename: B
authors.initials: B
authors.lastname: Erokwu
authors.forename: I A
authors.initials: IA
authors.lastname: Dreshaj
mesh_terms: D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D005289:Ferrets; D018738:Hexamethonium / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology; D009475:Neurons, Afferent / Q000737:chemistry / Q000378:metabolism*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000166:cytology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000096:biosynthesis; D011978:Receptors, Nicotinic / Q000032:analysis / Q000096:biosynthesis*; D012018:Reflex / Q000502:physiology; D017552:Solitary Nucleus / Q000166:cytology*; D014132:Trachea / Q000294:innervation* / Q000502:physiology
chemical_list: D018738:Hexamethonium; D018733:Nicotinic Antagonists; D016760:Proto-Oncogene Proteins c-fos; D011978:Receptors, Nicotinic