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Hypersensitivity of pulmonary C fibre afferents induced by cationic proteins in the rat

Qihai Gu and Lu-Yuan Lee

1. Airway administration of synthetic cationic proteins, poly-L-lysine (PLL) and poly-L-arginine (PLA), is known to induce bronchial hyper-responsiveness, and an involvement of bronchopulmonary C fibre activation has been suggested. In this study we investigated the effects of PLL and PLA on single-unit pulmonary vagal C fibre afferents in anaesthetized, open-chest rats.
2. Intratracheal (I.T.) instillation of PLL or PLA activated C fibre endings in a dose-dependent manner; for example, a high dose of PLL (50 µg in 0.1 ml) had a sporadic but intense stimulatory effect on these afferents. The augmented C fibre activity slowly declined but remained elevated even after 120 min.
3. Intratracheal instillation of PLL or PLA greatly enhanced the sensitivities of pulmonary C fibres to both lung inflation and chemical stimuli (e.g. capsaicin); for example, the change in fibre activity in response to constant-pressure lung inflation (tracheal pressure (P_t) = 30 cmH₂O; 10 s duration) increased by ~6-fold after PLL instillation.
4. When administered by intravenous injection or instilled into a different region of the lung, PLL or PLA, even at a higher dose, failed to have any effect on the C fibre endings.
5. The stimulatory and sensitizing effects of PLL or PLA were completely nullified when their cationic charges were neutralized with low molecule weight heparin.
6. In conclusion, I.T. instillation of synthetic cationic proteins causes an intense stimulatory effect on pulmonary C fibres and potentiates their sensitivities to both lung inflation and chemical stimuli. These effects are probably generated by an interaction between the cationic charges carried by these proteins and the airway mucosa.

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