Neuroanatomical relationships of substance P‐immunoreactive intrapulmonary C‐fibers and nicotinic cholinergic receptors

Abstract

Previous studies have suggested that sensory mechanisms may be important components of addiction to, and withdrawal from, cigarette smoking. The sensory and respiratory responses to nicotine are mediated, in part, by bronchopulmonary C-fiber afferents. Nicotine has a direct stimulatory effect on pulmonary sensory neurons, and nicotinic cholinergic receptors (nAChRs) composed of various combinations of alpha and beta subunits are known to be present in pulmonary ganglia. At the subcellular level, however, little is known about expression of nAChRs on sensory fibers in the intrapulmonary airways. The present study was therefore designed to evaluate the expression of nAChRs on a subset of intrapulmonary sensory nerve endings known to exhibit immunoreactivity for substance P (SP). The presence of nAChR subunits was first confirmed at the mRNA and protein levels in rat lung tissues by using RT-PCR and Western blot techniques. Then, double labeling of SP-immunoreactive (-IR) C-fibers and different nAChR subunits was performed. Alpha2, alpha3, alpha4, alpha5, alpha7, and beta2 subunits were detected at all levels of the intrapulmonary airways; including bronchi, terminal and respiratory bronchioles, alveolar walls, and alveolar macrophages. None of the nAChR subunits studied was expressed by the SP-IR C-fibers. However, SP-expressing C-fibers were observed in close proximity to and intermingling with nAChR-expressing airway epithelial cells. The close proximity of C-fibers to nAChR-expressing airway epithelial cells suggests that a component of nicotinic stimulation of SP-IR C-fiber afferents may be mediated by endogenous chemical substances released by nAChR-expressing epithelial cells.

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

“…Nicotine associated with cigarette smoking activates lung rapidly adapting receptors and pulmonary C-fiber afferents through receptors believed to be located on free nerve endings (Lee et al 2007). We have recently demonstrated the expression of multiple nicotinic acetylcholine receptor (nAChR) subtypes by epithelial cells, but not by the substance P (SP) immunoreactive (IR) C-fiber terminals of the intrapulmonary airways (Dehkordi et al 2009). Whether nAChR expressing cells of the airway epithelium function as chemoreceptor cells and participate in the sensory signal transduction pathway of nicotine is not known.…”

“…Whether nAChR expressing cells of the airway epithelium function as chemoreceptor cells and participate in the sensory signal transduction pathway of nicotine is not known. Previous anatomical studies have demonstrated the presence of solitary chemosensory cells (SCCs) throughout nasal (Finger et al 2003), bronchial and bronchiolar airway epithelial cells (Merigo et al 2005(Merigo et al , 2007. SCCs of the airway epithelium have been identified using antibody against α-gustducin, a GTP-binding α subunit of the heterotrimeric nucleotide-binding protein (G protein) found in taste receptor cells (Zancanaro et al 1999;Finger et al 2003;Sbarbati and Osculati 2003;Tizzano et al 2006;Merigo et al 2007).…”

“…Previous anatomical studies have demonstrated the presence of solitary chemosensory cells (SCCs) throughout nasal (Finger et al 2003), bronchial and bronchiolar airway epithelial cells (Merigo et al 2005(Merigo et al , 2007. SCCs of the airway epithelium have been identified using antibody against α-gustducin, a GTP-binding α subunit of the heterotrimeric nucleotide-binding protein (G protein) found in taste receptor cells (Zancanaro et al 1999;Finger et al 2003;Sbarbati and Osculati 2003;Tizzano et al 2006;Merigo et al 2007). SCCs have also been identified by phospholipase C-β2 (PLC-β2), an essential enzyme for taste transduction and by bitter responsive type 2 receptors (T2Rs) known to be present in type II taste receptor cells (Finger et al 2003;Merigo et al 2007).…”

“…Sensory and environmental cues are known to play an important role in the reinforcing effects of nicotine (Mangold et al 2008;Rose 2008aRose ,b, 2009McClernon et al 2009). Bitter taste is one of the sensory perceptions elicited by tobacco consumption and may contribute to nicotine dependence (Mangold et al 2008).…”

First report of vagal ischemia induced lung immune componenet infarct following subarachnoid hemorrhage: experimental study

“…One of the other important causes of breathing disability at the beginning of SAH is bronchoconstriction resulting from ischemic vagal conveying lymphatic products into the lungs. The lymphatic system of the lungs and the lymphatic vasculature have a major role in body homeostasis and immune surveillance and in the pathogenesis of lung disease (13,31). The cholinergic anti-inflammatory pathway is a neurophysiological mechanism that regulates the immune system of lungs (16).…”