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Cordyceps militaris extract stimulates Clâ» secretion across human bronchial epithelia by both CaÂ²âº- and cAMP-dependent pathways
- Fung, Jacky Chun-kit, Yue, Grace Gar-Lee, Fung, Kwok-pui, Ma, Xin, Yao, Xiao-qiang, Ko, Wing-hung
- Journal of ethnopharmacology 2011 v.138 no.1 pp. 201-211
- Cordyceps, Ophiocordyceps sinensis, adenylate cyclase, cAMP-dependent protein kinase, cyclic AMP, cystic fibrosis, epithelial cells, epithelium, humans, ion transport, secretion, signal transduction, traditional medicine
- ETHNOPHARMACOLOGICAL RELEVANCE: The caterpillar fungus Cordyceps militaris (CM; Clavicipitaceae) is a well-known traditional Chinese medicine that can be artificially cultivated on a large scale. We have previously demonstrated that its stimulatory action on ion transport in human airway epithelia is similar to Cordyceps sinensis (Clavicipitaceae), which has been traditionally used to treat respiratory diseases. AIM OF THE STUDY: To investigate the signal transduction mechanism(s) underlying CM-induced ion transport activity in cultured human bronchial epithelia. MATERIALS AND METHODS: 16HBE14o-, a human bronchial epithelial cell line, was used to study the regulation of ion transport by the water extract of CM. CM extract was added to the apical or basolateral aspect of the epithelia. In subsequent experiments, different Clâ» channel and Kâº channel blockers, adenylate cyclase and protein kinase A (PKA) inhibitors, and an intracellular CaÂ²âº chelator were used to examine the involvement of apical Clâ» and basolateral Kâº channels in mediating CM-induced Clâ» secretion and the underlying signal transduction mechanism(s). PKA activity was also measured in 16HBE14o- cells. RESULTS: CM stimulated Clâ» secretion across 16HBE14o- monolayers in a dose-dependent manner. Clâ» secretion could be inhibited by apical application of the cystic fibrosis transmembrane conductance regulator (CFTR) Clâ»channel blocker and the calcium-activated Clâ» channel (CaCC) blocker. Clâ» secretion was sensitive to basolateral application of different Kâº channel blockers. Similar inhibitory patterns were obtained in nystatin-permeabilized epithelia. The CM-induced Clâ» secretion could be inhibited by adenylate cyclase and PKA inhibitors as well as an intracellular CaÂ²âº chelator. Data from the PKA assay suggested that CM extract caused a significant increase in PKA activity compared with untreated control epithelia. CONCLUSIONS: These results suggest that CM extract stimulated Clâ» secretion across human bronchial epithelia, possibly via apical CFTR and CaCC, and the basolateral Kâº channels are involved in driving apical Clâ» exit. The underlying signal transduction mechanisms involve both cAMP- and CaÂ²âº-dependent pathways.