Hypersensitivity of bronchopulmonary C-fibers induced by airway mucosal inflammation: cellular mechanisms.
Stimulation of vagal bronchopulmonary C-fibers induces bronchoconstriction and hypersecretion of mucus, and is either directly or indirectly involved in eliciting cough reflex. Our recent studies have shown that the excitability of these afferents is markedly elevated in experimental conditions involving acute injury or inflammation of airway mucosa (e.g. after exposure to ozone), and cyclo-oxygenase metabolites of arachidonic acid locally released in the airways may contribute partially to the C-fiber hypersensitivity. Among the various prostanoids, prostaglandin E(2) administered by slow infusion augmented the responses of pulmonary C-fibers to both lung inflation and various chemical stimulants in anesthetized rats. The PGE(2)-induced hypersensitivity of these sensory nerves could also be demonstrated in cultured neurons using the whole-cell perforated patch-clamp recording technique; PGE(2) perfusion markedly and reversibly increased both the magnitude of inward current (in voltage-clamp mode) and the number of action potentials (in current-clamp mode) evoked by capsaicin in the small-diameter nodose and jugular ganglion neurons isolated from adult rats. Moreover, PGE(2) enhanced the membrane excitability of these neurons in their response to injected current pulses and voltage steps. In conclusion, the sensitizing effect is caused by a direct action of PGE(2) on pulmonary C-fibers, and the cAMP/protein kinase A transduction cascade is probably involved.
Lee
Lu-Yuan
LY
Department of Physiology, University of Kentucky Medical Center, Lexington, Kentucky, 40536-0298, USA. lylee@pop.uky.edu
Kwong
Kevin
K
Lin
You Shuei
YS
Gu
Qihai
Q
D000818:Animals; D001980:Bronchi / Q000294:innervation / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D002478:Cells, Cultured; D003371:Cough / Q000503:physiopathology*; D007249:Inflammation / Q000503:physiopathology; D008168:Lung / Q000294:innervation / Q000503:physiopathology*; D009092:Mucous Membrane / Q000503:physiopathology; D009412:Nerve Fibers / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology; D051381:Rats