Calcium-activated chloride channels（CaCCs） are the crucial regulators of transepithelial fluid secretion, smooth muscle contraction and sensory transduction. Recently, compelling evidence has indicated that TMEM16A（ANO1 or anoctamin-1） is a bona fide calcium-acvtivated chloride channel. A few small molecule CaCCs regulators are available for functional and therapeutic studies. We screened 126 natural compounds from Chinese herbs. Screening was performed with an iodide influx assay in Fischer rat thyroid epithelial cells to coexpress ANO1 and an iodide-sensitive fluorescent indicator（EYFP-H148Q/I152L）. Imperatorin, a coumarin compound, was identified to inhibit ANO1-mediated chloride transport activated by multiple calcium-elevating agonists. The inhibitory effect is dose-dependent with IC50～14.63 μmol/L. Interestingly, imperatorin activated CFTR chloride channel with EC50～35.52 μmol/L. The adverse effects of imperatorin on CaCC and CFTR chloride channels will make it useful in pharmacological dissection of chloride transport in airway and intestinal epithelium. Further studies are required to evaluate the therapeutic effects of imperatorin on hypertension, asthma and certain tumors.
Taurine is concentrated in glial cells in the hypothalamus and released in an osmo-dependent manner through volume-sensitive anion channels. Released tanrine acts on glycine receptors on vasopressin neurons to control vasopressin secretion. Water channel AQP4 is abundant in astrocytes in osmosensory areas such as the supraoptic nucleus of hypothalamus. An HPLC-based method was established to quantify taurine release from isolated hypothalamus tissues in wildtype and AQP4 knockout mice. Under the basal condition, there was no difference in taurine release from AQP4^＋/＋ and AQP4^-/- hypothalamuses. Taurine release from AQP4^-/- hypothalamus under hypoosmotic stimulation was significantly lower than that from AQP4^＋/＋ mice. AQP4 expression in the glial cells of the hypothalamus may play an important role in osmoregulation oftaurine release and subsequent vasopressin secretion.
ZHANG Hong-guo XIAO Ying-hong YANG Long-fei SU Wei-heng GUAN Xin-gang WANG Yu FENG Xue-chao MA Tong-hui
