Dual Sensory Innervation of Pulmonary Neuroepithelial Bodies

Abstract

The characteristics of the different populations of sensory nerve terminals that selectively contact pulmonary neuroepithelial bodies (NEBs) in rat lungs were investigated after chemical denervation with capsaicin and compared with control lungs. Vagal calbindin D28k and P2X(3) purinoceptor immunoreactive (IR) afferent nerve terminals contacting NEBs appeared to have their origin in the nodose ganglion. Thick CB/P2X(3)-IR nerve fibers were seen to be myelinated and to lose their myelin sheaths just before branching and protruding intraepithelially between the NEB cells. This vagal sensory component of the innervation of NEBs was not affected by capsaicin nor expressed capsaicin receptors (vanilloid receptor subtype 1). A second sensory nerve fiber population that selectively innervates pulmonary NEBs in the rat lung consists of thin unmyelinated nonvagal substance P/calcitonin gene-related peptide IR nerve fibers, contacting mainly the basal pole of pulmonary NEBs, and having their origin in dorsal root ganglia. In concordance with vanilloid receptor 1 expression on these nerve terminals, the spinal sensory substance P/calcitionin gene-related peptide-IR component of the innervation of NEBs was depleted by systemic capsaicin treatment. The complex sensory innervation pattern of pulmonary NEBs characterized in the present study strongly suggests that, physiologically, pulmonary NEBs represent a group of intraepithelial receptors that may be able to accommodate various local and central reflex actions, in relation to both chemo- and mechanosensory stimuli.

Innervation of Pulmonary Neuroendocrine Cells and Neuroepithelial Bodies in Developing Rabbit Lung

“…Other studies reported variable innervation of NEBs in adult rat lungs with a subpopulation lacking neural connections (Larson et al 2003). These were interpreted as representing possible different NEBs functional subgroups, i.e., innervated NEB functioning as chemoreceptors, whereas those without innervation representing endocrine/paracrine cells (Adriaensen et al 2003;Brouns et al 2003;Larson et al 2003). However, the possibility that this apparent lack of innervation in some NEBs may be due to technical problems or may reflect immature or senescent NEBs has not been excluded.…”

“…Dennervation and neural tracing experiments in the rabbit and the rat revealed that NEBs are innervated predominantly by vagal afferent fibers derived from the nodose ganglion (Lauweryns and Van Lommel 1986;Adriaensen et al 1998;Van Lommel et al 1998). Recent studies using multilabel IHC and confocal microscopy have identified complex innervation of NEBs in rat lungs (Adriaensen et al 2003;Brouns et al 2003). These studies identified three distinct sources of NEB innervation in rat lung, i.e., vagal afferents immunoreactive for calbindin D21k and P2/X3 originating in nodose ganglion, a rich network of CGRP-immunoreactive nerves derived from the dorsal root ganglia, and an nNOS-immunoreactive component derived from intrinsic bronchial ganglia.…”

Pathophysiology and Therapeutic Potential of Purinergic Signaling

“…It has been suggested that ventilator-induced lung injury may involve stretch-associated release of ATP from neuroepithelial cell bodies (Brouns et al, 2000(Brouns et al, , 2003Rich et al, 2003) and may therefore be a therapeutic target for this condition.…”

Quantification of Neuroepithelial Bodies and Their Innervation in Fawn-Hooded and Wistar Rat Lungs

“…NADPH oxidase was suggested to be the oxygensensing molecule (13,14). Most likely, nerve fiber populations selectively innervating NEBs are involved in the reaction to hypoxia (15)(16)(17). Based on an ultrastructural analysis of rabbit NEBs, morphologically afferent-like as well as efferent-like nerve endings innervating NEBs were reported to be involved in the reaction of NEBs to acute hypoxia (18,19).…”

“…An intraepithelial vagal sensory innervation of NEBs, with origin in the nodose ganglion (20), appeared to be myelinated and was characterized by a calbindin D28k (CB) immunostaining (16) and the expression of purinergic P2X 3 receptors (11). A second sensory, capsaicin-sensitive, and calcitonin gene-related peptide (CGRP)/Substance P (SP)-immunoreactive (IR) innervation of NEBs, was shown to have a nonvagal origin (16,20). Retrograde tracing experiments suggested a spinal origin for the latter sensory nerve fiber population (21).…”