Airway-related vagal preganglionic neurons express multiple nicotinic acetylcholine receptor subunits

Abstract

Nicotine acting centrally increases bronchomotor tone and airway secretion, suggesting that airwayrelated vagal preganglionic neurons (AVPNs) within the rostral nucleus ambiguus (rNA) express nicotinic acetylcholine receptors (nAChRs). In the present study, we examined the three main functionally characterized subtypes of nAChRs in the CNS, the α7 homomeric and α4β2 heteromeric receptors. First, we characterized the expression of these subunits at the message (mRNA) and protein levels in brain tissues taken from the rNA region, the site where AVPNs are located. In addition, double labeling fluorescent immunohistochemistry and confocal laser microscopy were used to define the presence of α7, α4, and β2 nAChRs on AVPNs that were retrogradely labeled with cholera toxin h subunit (CTb), injected into the upper lung lobe (n = 4) or extrathoracic trachea (n = 4). Our results revealed expression of all three studied subunits at mRNA and protein levels within the rNA region. Furthermore, virtually all identified AVPNs innervating intrapulmonary airways express α7 and α4 nAChR subunits. Similarly, a majority of labeled AVPNs projecting to extrathoracic trachea contain α7 and β2 subunits, but less than half of them show detectable α4 nAChR traits. These results suggest that AVPNs express three major nAChR subunits (α7, α4, and β2) that could assemble into functional homologous or heterologous pentameric receptors, mediating fast and sustained nicotinic effects on cholinergic outflow to the airways.

Co-expression of nAChRs and molecules of the bitter taste transduction pathway by epithelial cells of intrapulmonary airways

“…The sections were first processed for detection of the α3, α4, α5, α7 and β2 subunits of nAChRs using the Tyramide Signal Amplification (TSA) Fluorescence System (PerkinElmer Life Sciences, Boston, MA) as previously described (Dehkordi et al 2006(Dehkordi et al , 2007. Endogenous peroxidase activity was quenched before the immunostaining by exposing the sections to 0.1 M PBS containing 0.3% hydrogen peroxide for 30 min.…”

Effects of Preconditioning on the Resistance to Acute Hypobaric Hypoxia and Their Correction with Selective Antagonists of Nicotinic Receptors

“…Homomeric α 7 receptors and heteromeric α 4 β 2 receptors are the most widely distributed subtypes of NCR in the brain. For example, they are expressed in neurons of the medulla oblongata that play a role in the regulation of breathing and cardiovascular function [3,4]. Subtype α 3 β 4 receptors are also identifi ed in the medulla oblongata.…”

“…NCR are expressed in all parts of the system for autonomic regulation of respiration and blood supply (from peripheral chemoreceptors and mechanoreceptors to sensory neurons and motoneurons in CNS) [3,5,6,10,11,15]. Homomeric α 7 receptors and heteromeric α 4 β 2 receptors are the most widely distributed subtypes of NCR in the brain.…”

“…A series of studies were devoted to evaluating the receptor specifi city of cholinergic regulation in various organs. Vasodilation of major cerebral vessels and abdominal vessels is specifi cally realized via α 7 NCR [15] and α 3 β 4 receptors [3], respectively. The airway tone is regulated by α 7 and α 4 β 2 receptors, but not by α 3 -containing subtypes of NCR [3].…”

“…Vasodilation of major cerebral vessels and abdominal vessels is specifi cally realized via α 7 NCR [15] and α 3 β 4 receptors [3], respectively. The airway tone is regulated by α 7 and α 4 β 2 receptors, but not by α 3 -containing subtypes of NCR [3]. The sinocarotid nerve receives information from the carotid arteries via α 3 -containing NCR and, to a lesser extent, via α 7 receptors [9].…”