Cigarette smoke-induced irritation in the airways in relation to peptide-containing, capsaicin-sensitive sensory neurons.
Cigarette smoke-induced irritation of the nasal and tracheal mucosa induces both protective reflexes and vascular reactions (protein extravasation). The vapor phase of the smoke rather than the particulate phase containing nicotine seems to be mainly responsible for these reactions in the guinea pig and rat, and nicotine-free cigarettes also caused marked irritation. The vapor-phase components activate a specific type of sensory nerves, presumably belonging to the C-fibre group, which are sensitive to capsaicin. These nerves contain tachykinins and CGRP in their peripheral branches within the respiratory epithelium, around blood vessels, and in the bronchial smooth muscle layer. Tachykinins and CGRP are released from these sensory nerves upon acute chemical irritation by, for instance, capsaicin. Tachykinins are potent vasodilating agents and induce plasma-protein extravasation and bronchoconstriction, while CGRP mainly evokes vasodilatation. After pretreatment with high doses of capsaicin, tachykinins and CGRP are depleted from the sensory nerves which subsequently degenerate. The irritation in the nasal mucosa and the tracheal protein extravasation induced by cigarette smoke are absent in capsaicin-pretreated animals, while the mechanical sensitivity and efferent nerve function remain. Also the allergic reaction is reduced after capsaicin treatment, indicating that cigarette smoke and the mediators of the allergen response activate a common pathway.
Lundberg
J M
JM
Department of Pharmacology, Karolinska Institute, Stockholm, Schweden.
Martling
C R
CR
Lundblad
L
L
D000344:Afferent Pathways / Q000503:physiopathology; D000403:Airway Resistance; D000818:Animals; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin / Q000494:pharmacology*; D002415:Cats; D006168:Guinea Pigs; D009297:Nasal Mucosa / Q000294:innervation*; D009479:Neuropeptides / Q000502:physiology*; D051381:Rats; D011984:Sensory Receptor Cells / Q000503:physiopathology*; D012907:Smoking / Q000503:physiopathology*; D012912:Sneezing; D015320:Tachykinins / Q000502:physiology; D014132:Trachea / Q000294:innervation*; D014630:Vagus Nerve / Q000503:physiopathology*
D009479:Neuropeptides; D015320:Tachykinins; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin