Nerve fibres displaying immunoreactivity to calcitonin gene-related peptide (CGRP) are abundantly distributed in the respiratory tract of man, dog, cat, guinea-pig, rat and mouse. Numerous fine, beaded CGRP fibres were seen in the middle ear mucosa, and a moderate supply was found in the ear drum. In the nasal mucosa and in the wall of the Eustachian tube CGRP fibres occurred around blood vessels, arteries in particular. A conspicuously rich supply of CGRP fibres was seen beneath and within the epithelium. In addition, a few fibres were seen in smooth muscle bundles and close to sero-mucous glands. In the tracheo-bronchial wall CGRP fibres were distributed beneath and within the epithelium, in vascular and non-vascular smooth muscle and sometimes close to small glands. A few CGRP-immunoreactive endocrine-like cells were, in addition, distributed in the tracheal epithelium of cat, rat and mouse. The trigeminal, spinal and nodose ganglia, studied in rats and guinea-pigs, harboured numerous CGRP-immunoreactive nerve cell bodies. The cervical sympathetic ganglia were devoid of immunoreactive neuronal perikarya. Surgical and chemical (6-hydroxydopamine treatment) sympathectomy did not affect the number and distribution of CGRP fibres. The distribution of CGRP fibres in the respiratory tract suggests that CGRP may take part in sensory transmission. In addition, CGRP may affect the regulation of local blood flow, smooth muscle tone and glandular secretion.
"However, the distribution of SP-IR and CGRP-IR NFs in the nerve roots and blood vessels of the human TTM has not previously been reported. Moreover, the presence and distribution of CGRP-IR NFs indicate sensory transmission and the regulation of local blood flow, smooth muscle tone and glandular secretion in the upper and lower respiratory tract of several mammals, including humans . Previous studies have examined local regional sites; we aimed to study distribution of neurovascular insertion sites such as sensory nerve fiber , which indicate morphological and functional properties of middle ear muscles. "
[Show abstract][Hide abstract] ABSTRACT: Substance P-immunoreactive nerve fiber (SP-IR NF) and calcitonin gene-related peptide-immunoreactive nerve fiber (CGRP-IR NF) are important mediators of neurogenic inflammation and blood supply. SP-IR and CGRP-IR NFs in the tensor tympani muscle (TTM) of the human middle ear have yet to be described. In this study, the TTM, tympanic membrane, malleus in the middle ear and tensor veli palatini muscle (TVPM) were examined by whole-mount immunohistochemistry in tissue from Japanese subjects. Thirteen human cadavers (ranging in age from 46 to 90 years) were used in this study. SP-IR and CGRP-IR NFs were primarily found on vessels at the origin, insertion and belly of the surface of the TTM and on the internal surface of the tympanic membrane. These neural factors were also detected on the surface of the malleus and the insertion of the TVPM. Therefore, our results indicate that existence of the SP-IR and CGRP-IR NFs of the TTM and the TVPM may reflect muscle properties involved in pain or inflammation of the middle ear.
Archives of Oto-Rhino-Laryngology 04/2013; 271(5). DOI:10.1007/s00405-013-2469-1 · 1.55 Impact Factor
"Additionally, all nerves studied seemed to have bilateral effects in the trachea but vagus nerves appeared to have a unilateral effect in the bronchi (McDonald et al., 1988). Moreover, it has been shown that mast cells are present in close proximity to SP and CGRP containing sensory nerves in the trachea of mammals (Lundberg et al., 1984, Uddman et al., 1985). SP released by sensory nerves in the trachea activates local mast cells (Maggi, 1997), leading to plasma protein extravasation. "
[Show abstract][Hide abstract] ABSTRACT: An up-regulation of the sensory neural pathways in the lung has been implicated in asthma and chronic obstructive pulmonary disease (COPD) and is thought to contribute to mucus hypersecretion, an essential feature of both diseases. The aim of this study was to assess non-invasively the acute effects (up to 60 min) of sensory nerve stimulation by capsaicin in the lung, using magnetic resonance imaging (MRI).
Male Brown Norway rats were imaged prior to and 10, 30 and 60 min after intra-tracheal challenge with capsaicin (30 microg kg(-1)) or vehicle (0.5% ethanol solution). In subsequent studies, pre-treatment with the transient receptor potential vanilloid (TRPV)-1 antagonist, capsazepine; the dual neurokinin (NK) 1 and NK2 receptor antagonist, DNK333 and the mast cell stabilizer, di-sodium cromoglycate (DSCG) was used to modulate the effects of capsaicin.
Diffuse fluid signals were detected by MRI in the lung as early as 10 min after capsaicin, remaining constant 30 and 60 min after treatment. Broncho-alveolar lavage (BAL) fluid analysis performed 60 min after capsaicin revealed increased mucin concentration. Capsazepine (3.5 mg kg(-1)), DNK333 (10 mg kg(-1)) but not DSCG (10 mg kg(-1)) administered prophylactically were able to block the effect of capsaicin in the airways.
These observations suggest that the fluid signals detected by MRI after capsaicin administration reflected predominantly the release of mucus following activation of sensory nerves. They point to the opportunity of non-invasively assessing with MRI the influence of neuronal mechanisms in animal models of asthma and COPD.
British Journal of Pharmacology 05/2007; 150(8):1022-30. DOI:10.1038/sj.bjp.0707168 · 4.84 Impact Factor
"Although the antiserum against CGRP does not always react against all of the C-cells, the expression of CGRP in C-cells is confirmed by a study using ISH techniques (van Lieshout et al. 1995). On the other hand, IHC studies have revealed that basal granulated cells in respiratory tracts produce CGRP (Uddman et al. 1985; Lauweryns and Van Ranst 1987; Keith and Ekman 1988, 1990). In human (Tsutsumi 1989; Stahlman and Gray 1993) and rat (Shimosegawa and Said 1991), it has been reported that calcitonin is expressed in some CGRP-positive basal granulated cells "
[Show abstract][Hide abstract] ABSTRACT: We examined immunocytochemical localization of the prohormone convertases, PC1 and PC2, in the thyroid gland and respiratory tract of the adult mouse using the indirect enzyme- and immunogold-labeled antibody methods for light and electron microscopy, respectively. In the thyroid gland, PC1- and/or PC2-immunoreactive cells were cuboidal, scattered in the follicular epithelium and in the interfollicular spaces. When serial sections were immunostained with anti-calcitonin, anti-PC1, anti-calcitonin-gene-related-peptide (CGRP), and anti-PC2 sera, respectively, localization of both PC1 and PC2 was restricted to the calcitonin/CGRP-producing parafollicular cells. In the respiratory tract, only PC1 immunoreactivity was observed in the basal granulated neuroendocrine cells, which were scattered in the tracheal epithelium. Consecutive sections immunostained with anti-PC1 and anti-CGRP sera showed that a subpopulation of these PC1-immunoreactive cells contained CGRP. Double immunogold electron microscopy of the thyroid parafollicular cells revealed that calcitonin- and/or CGRP-immunopositive secretory granules were also labeled with both PC1 and PC2. These findings suggest that procalcitonin is proteolytically cleaved by PC2 alone or by PC2 together with PC1, and that the proCGRP is cleaved by PC1.
Journal of Histochemistry and Cytochemistry 08/2002; 50(7):903-9. DOI:10.1177/002215540205000704 · 1.96 Impact Factor
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