Active Ingredients Of Traditional Chinese Medicine Regulate The Function Of CaCCs

Calcium-activated chloride channel(CaCCs) which is named for it can be activated by cytosolic sub-micromolar Ca2+, which are widely distributed in various organisms and involved in such as: across epithelial ion transport, olfactory transmission, smooth muscle contraction, the feeling of pain, visual signal conversion, control the excitement of neurons, and other physiological activities. Dysfunction of CaCCs will lead to serious consequences: high blood pressure, Sjogren’s syndrome, airway hyperreactivity, lung diseases and some tumors. CaCCs has become one of the important drug targets. It has been identified that TMEM16A/B are the molecular basis of CaCCs. Identification of TMEM16A/B will show light on treatments on Ca CCs-related diseases.Chinese medicine is a treasure of mankind, the proliferation of prosperity for the Chinese nation and makes an important contribution to healthy living, contains a wealth of scientific connotation. Searching CaCCs regulators from the active ingredients of traditional Chinese medicine is not only to save the selection time, but also rich scientific content of traditional Chinese medicine, as well as reduce prejudice to Chinese medicine in the West. In this study, we mainly used patch-clamp electrophysiology techniques and fluorescence microscopy imaging techniques for screening regulators of CaCCs from the active ingredients of traditional Chinese medicine, aimed at finding the activity of natural compounds to regulate CaCCs. The main contents are as follows:(1) Based on prescriptions, we determined nineteen canditates as follows: scopoletin, stachydrine, resveratrol, rhein, paeoniflorin, quercetin, papaverine, berberine, etc. The fluorescence data identified two from ninteen ingredients which many activate CaCCs channel.(2) Emodin, not resveratrol, can increase the intracellular concentration of Ca2+ by release the Ca2+ from the calcium stores.(3) Resveratrol activates CaCC channels by direct interactions with channel. Emodin opens CaCCs by elevation of intracellular calcium ion concentration.(4) At organ level, resveratrol can promote the intestinal muscle contraction by activate TMEM16 A channels, and this activity can be inhibited by CaCCs inhibitor CaCCinh-A01.(5) There are two analogues of resveratrol: acetyl-trans-resveratrol and Trimethoxystilbene. Compaired with resveratrol, those two analogues can’t open CaCCs at all which indicates that the hydroxyl groups of resveratrol play key roles in activating CaCCs.