title: Neurochemical characterisation of sensory receptors in airway smooth muscle: comparison with pulmonary neuroepithelial bodies.
abstract: Descriptions of morphologically well-defined sensory airway receptors are sparse, in contrast to the multiplicity of airway receptors that have been identified electrophysiologically. The present study aimed at further determining the location, morphology and neurochemical coding of subepithelial receptor-like structures that have been sporadically reported in the wall of large diameter airways. The results were compared with those obtained for pulmonary neuroepithelial bodies (NEBs), which are complex intraepithelial sensory airway receptors. Multiple immunocytochemical staining showed branching laminar subepithelial receptor-like endings, which were found to intercalate in the smooth muscle layer of intrapulmonary conducting airways in rats. Because of the consistent intimate association with the airway smooth muscle, the laminar terminals will further be referred to as 'smooth muscle-associated airway receptors (SMARs)'. SMARs were characterised by their Na(+)/K(+)-ATPase alpha3, vesicular glutamate transporter 1 (VGLUT1) and VGLUT2-immunoreactivity, expression of the ATP receptor P2X(3), and the presence of calcium-binding proteins. Nerve fibres giving rise to SMARs were shown to be myelinated and to have a vagal origin. Interestingly, the neurochemical coding and receptor-like appearance of SMARs appeared to be almost identical to at least part of the complex vagal sensory terminals in NEBs. Intraepithelial nerve endings in pulmonary NEBs were indeed also shown to originate from myelinated vagal afferent nerve fibres, and to express Na(+)/K(+)-ATPase alpha3, VGLUT1, VGLUT2, P2X(3) and calcium-binding proteins. Since several of the latter proteins have been reported as markers for mechanoreceptor terminals in other organs, both SMARs and the vagal nodose nerve terminals in NEBs seem good candidates to represent the morphological counterparts of at least subsets of the extensive population of physiologically characterised myelinated vagal airway mechanoreceptors. The observation that SMARs and NEBs are regularly found in each other's immediate neighbourhood, and the very similar characteristics of their nerve terminals, point out that the interpretation of electrophysiological data based on 'local' stimuli should be made with great caution.
authors.affiliation: Laboratory of Cell Biology and Histology, Department of Biomedical Sciences, University of Antwerp, Groenenborgerlaan 171, 2020, Antwerp, Belgium.
authors.forename: Inge
authors.initials: I
authors.lastname: Brouns
authors.forename: Isabel
authors.initials: I
authors.lastname: Pintelon
authors.forename: Ian
authors.initials: I
authors.lastname: De Proost
authors.forename: Roel
authors.initials: R
authors.lastname: Alewaters
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Timmermans
authors.forename: Dirk
authors.initials: D
authors.lastname: Adriaensen
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001980:Bronchi / Q000294:innervation / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002628:Chemoreceptor Cells / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D008465:Mechanoreceptors / Q000378:metabolism*; D009130:Muscle, Smooth / Q000166:cytology / Q000294:innervation / Q000378:metabolism*; D009411:Nerve Endings / Q000166:cytology / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000378:metabolism; D046568:Neuroepithelial Bodies / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058477:Receptors, Purinergic P2X3; D012137:Respiratory System / Q000166:cytology* / Q000294:innervation / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; C546410:P2rx3 protein, rat; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; C493475:Slc17a6 protein, rat; C493466:Slc17a7 protein, rat; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D000254:Sodium-Potassium-Exchanging ATPase