| [ Summary ] |
Several people experience stress in daily life due to constipation. Several drugs that differ mechanistically have been used to mitigate unpleasant symptoms of constipation including Japanese herbal (Kampo) medicines. However, their mechanisms of action are often not well understood. Recently, there has been substantial advancement in this respect of Chinese medicine Junchoto (JCT)/Mashiningan (MNG) empirically prescribed for chronic constipation. In functional analyses at both a cellular and tissue level, JCT/MNG dose-dependently induced channel activities with biophysical and pharmacological features typical of CFTR. Treatment with each adenylate cyclase (AC)-inhibitor, CFTR inhibitor, and siRNA targeting CFTR abolished the JCT-induced channel activity, suggesting that JCT-induced elevated intracellular cAMP causes CFTR activation. Blockade of CFTR activity by the CFTR inhibitor, siRNA-knockdown of CFTR, or application of AC-inhibitor markedly reduced the degree of cell-volume decrease induced by JCT. Moreover, JCT induced Cl-efflux through the CFTR channel to promote water secretion, possibly through increased cAMP production. In this report, we discuss the action mechanisms of lubiprostone, which has recently attracted growing attention as a small intestinal irritant laxative with comparable effect to that of JCT. |