title: Catecholaminergic microcircuitry controlling the output of airway-related vagal preganglionic neurons.
abstract: In this study, we have investigated the ultrastructure and function of the catecholaminergic circuitry modulating the output of airway-related vagal preganglionic neurons (AVPNs) in ferrets. Immunoelectron microscopy was employed to characterize the nature of catecholaminergic innervation of AVPN at the ultrastructural level. In addition, immunofluorescence was used to examine the expression of the alpha(2A)-adrenergic receptor (alpha(2A)-AR) on AVPNs, and norepinephrine release within the rostral nucleus ambiguous (rNA) was measured by using microdialysis. Physiological experiments were performed to determine the effects of stimulation of the noradrenergic locus coeruleus (LC) cell group on airway smooth muscle tone. The results showed that 1) catecholaminergic nerve endings terminate in the vicinity of identified AVPNs but very rarely form axosomatic or axodendritic synapses with the AVPNs that innervate the extrathoracic trachea; 2) AVPNs express the alpha(2A)-AR; 3) LC stimulation-induced norepinephrine release within the rNA region was associated with airway smooth muscle relaxation; and 4) blockade of alpha(2A)-AR on AVPNs diminished the inhibitory effects of LC stimulation on airway smooth muscle tone. It is concluded that a noradrenergic circuit originating within the LC is involved in the regulation of AVPN activity within the rNA, and stimulation of the LC dilates the airways by the release of norepinephrine and activation of alpha(2A)-AR expressed by AVPNs, mainly via volume transmission.
authors.affiliation: Departments of Physiology and Biophysics and Pharmacology, Howard University College of Medicine, Washington, DC 20059, USA. mhaxhiu@howard.edu
authors.forename: Musa A
authors.initials: MA
authors.lastname: Haxhiu
authors.forename: Prabha
authors.initials: P
authors.lastname: Kc
authors.forename: Burim
authors.initials: B
authors.lastname: Neziri
authors.forename: Bryan K
authors.initials: BK
authors.lastname: Yamamoto
authors.forename: Donald G
authors.initials: DG
authors.lastname: Ferguson
authors.forename: V John
authors.initials: VJ
authors.lastname: Massari
mesh_terms: D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000502:physiology* / Q000648:ultrastructure; D002395:Catecholamines / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D005289:Ferrets; D006735:Horseradish Peroxidase; D007150:Immunohistochemistry; D008297:Male; D017551:Microdialysis; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009126:Muscle Relaxation; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology; D009415:Nerve Net / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D012137:Respiratory System / Q000294:innervation*; D014630:Vagus Nerve / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D002395:Catecholamines; D018341:Receptors, Adrenergic, alpha-2; D006735:Horseradish Peroxidase; D009638:Norepinephrine