Regulation of acid signaling by PAR2 in rat vagal pulmonary sensory nerves

Abstract

Protease‐activated receptor‐2 (PAR2) is involved in airway inflammation and airway hyperresponsiveness, the prominent features of asthma. Airway acidification has been consistently observed in airway inflammatory conditions, and is known to cause cardiorespiratory symptoms that are at least in part mediated through the activation of bronchopulmonary C‐fibers and the subsequent reflexes. This study was carried out to investigate the effect of PAR2 activation on the acid signaling in vagal pulmonary C‐fibers that may occur during airway inflammation. Our in‐vivo study showed that, in anesthetized and spontaneously breathing rats, intratracheal instillation of trypsin (1 mg/ml, 0.1 ml), an activator of PAR2, significantly enhanced the chemoreflex responses to right‐atrial injection of lactic acid. In isolated pulmonary C‐neurons, pre‐incubation of SLIGRL‐NH2 (100 μM, 2 min), a specific PAR2 activating peptide, markedly potentiated the whole‐cell inward currents evoked by extracellular acidification. In addition, a similar sensitizing effect was observed when the neurons were pretreated with 2‐furoyl‐LIGRL‐NH2 (100 μM, 2 min), a newly reported potent and selective PAR2 agonist. In conclusion, activation of PAR2 modulates the acid signaling in pulmonary C‐fiber sensory nerves, and the interaction may contribute to the pathogenesis of asthma and other airway inflammatory diseases. (Supported by grants from NIH, AHA and Parker B. Francis Fellowship in Pulmonary Research)