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Tachykinins and Neural Activity
The contribution of nonadrenergic, noncholinergic nerves to asthma pathogenesis remains poorly understood. Yoshihara and colleagues performed an in-depth pharmacologic study of the impact of cannabinoid receptors to inhibit capsaicin-induced contraction of tracheal rings in guinea pigs. In these studies, cannabinoid receptor 2 activation appeared to have the greatest inhibitory effects, primarily through diminishing release of tachykinins from sensory nerves, as cannabinoid receptor activation had no impact on neurokinin A–induced smooth muscle contraction. Further studies in other animal and human models with these cannabinoid receptor agonists should prove of interest.
A commonly used cancer drug, paclitaxel, known to induce severe hypersensitivity reactions, which include severe bronchospasm and respiratory distress, appears to induce these effects through sensory nerves, including both neurokinin (NK)-1 and NK2 pathways. In a study of paclitaxel in rats by Itoh and coworkers the authors could not induce the reaction in mast cell–deficient rats. However, both NK1 and NK2 receptor antagonists were effective in blocking the reactions. These findings might also suggest that other "presumed" mast cell–mediated reactions may be driven by sensory nerves.
Groneberg and coworkers determined the expression of transient receptor potential vanniloid 1 (TRPV-1) in the airways of patients with chronic persistent cough of diverse causes and with an enhanced capsaicin cough response. Airway mucosal biopsies were obtained by fiberoptic bronchoscopy in 29 patients with chronic cough and 16 healthy volunteers without a cough. Immunostaining for nerve profiles with antiprotein gene product-9.5 antibody showed no increase in nerve profiles in the airway epithelium of patients with chronic cough; however, with an anti–TRPV-1 antibody, there was a fivefold increase of TRPV-1–staining nerve profiles (p < 0.001). There was a significant correlation between capsaicin tussive response and the number of TRPV-1–positive nerves within the patients with cough. The findings indicate that TRPV-1 receptors may contribute to an enhanced cough reflex and the cough response in chronic persistent cough of diverse causes.
Citations 1-3 of 3 total displayed.
Increased Expression of Transient Receptor Potential Vanilloid-1 in Airway Nerves of Chronic Cough
- David A. Groneberg, Akio Niimi, Q. Thai Dinh, Borja Cosio, Mark Hew, Axel Fischer, and K. Fan Chung
Am. J. Respir. Crit. Care Med. 170: 1276 -1280. First published online as doi:10.1164/rccm.200402-174OC
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Cannabinoid Receptor Agonists Inhibit Sensory Nerve Activation in Guinea Pig Airways
- Shigemi Yoshihara, Hiroshi Morimoto, Yumi Yamada, Toshio Abe, and Osamu Arisaka
Am. J. Respir. Crit. Care Med. 170: 941 -946. First published online as doi:10.1164/rccm.200306-775OC
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Role of Sensory Nerve Peptides Rather than Mast Cell Histamine in Paclitaxel Hypersensitivity
- Yoshinori Itoh, Toshiaki Sendo, Toshio Hirakawa, Takeshi Goromaru, Shinya Takasaki, Hideaki Yahata, Hitoo Nakano, and Ryozo Oishi
Am. J. Respir. Crit. Care Med. 169: 113 -119. First published online as doi:10.1164/rccm.200307-901OC
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