Bakumondo-to, a traditional herbal medicine, stimulates phosphatidylcholine secretion, through the synergistic cross-talk between different signal transduction systems in alveolar type II cells

Abstract

Traditional herbal medicines, Kampo medicines in Japan, are composed of various herbs with ubiquitous pharmacological activities. We previously found that Bakumondo-to stimulates phosphatidylcholine (PC) secretion from alveolar type II cells. To define the regulatory mechanisms involving in the Bakumondo-to-induced PC secretion, we investigated the effect of Bakumondo-to on signal transduction systems in alveolar type II cells, Bakumondo-to-induced PC secretion was completely inhibited by each of H-89, H-7 or BAPTA-AM, protein kinase A (PKA), protein kinase C (PKC) or intracellular Ca2+ inhibitor. In addition, Bakumondo-to increased cellular cyclic AMP content and Ca2+ content, too. These results suggested that the secretagogue effect of Bakumondo-to may be coupled to the synergistic cross-talk between cyclic AMP- and Ca(2+)-dependent system. To investigate if there is cross-talk between different signaling systems in type II cells, we examined the combined effects of various secretagogues on PC secretion. The combination of terbutaline and PMA potentiated stimulation of secretion, although the effects of terbutaline with A23187, or PMA with A23187 were additive. This synergism seemed to be mediated by Ca2+ influx, because this combination significantly increased cellular Ca2+ content. These findings suggested that there is synergistic cross-talk between PKA- and PKC dependent signaling system in alveolar type II cells, and that Bakumondo-to may stimulate PC secretion through this cross-talk.