Occurrence and distribution of calcitonin gene-related peptide in the mammalian respiratory tract and middle ear.
ABSTRACT 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.
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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 · 4.99 Impact Factor
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ABSTRACT: Calcitonin gene-related peptide (CGRP) is a potent vasodilator peptide present in capsaicin-sensitive neurons innervating the respiratory tract. In this study, the autoradiographic distribution of [125I]CGRP binding sites was investigated in guinea pig airways. Extremely dense specific binding occurred over parenchymal tissue, with moderate specific binding over tracheal glands, the endothelium of pulmonary veins and arteries, and small blood vessels in the bronchial wall. The localization of binding sites for [125I]CGRP over blood vessels but not bronchial smooth muscle correlates well with the physiological actions of this peptide, although the function of the parenchymal sites is unknown. No significant difference in binding was seen in vehicle- or capsaicin-pretreated animals, suggesting that sites are not reliant on factors from capsaicin-sensitive neurons.Peptides 02/1995; 16(4):683-92. DOI:10.1016/0196-9781(95)00028-I · 2.61 Impact Factor
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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 · 1.61 Impact Factor