Aquaporins(AQPs) are molecular water channels that play important physiological roles in fluid trans-porting organs. The expression and function of AQPs in the immune system are largely unknown. CD 11 (a-d)/CD18 integrins are adhesion molecules expressed on leukocytes, which play a critical role in leukocyte adhesion, migration and host defense. In the present study, we discovered the expression of aquaporin-3(AQP3) on spleen CD1 lb positive cells, and the content of CDllb positive splenocytes in aquaporin 3-null mice is significantly decreased. Further analysis suggested remarkably decreased monocyte/macrophage subpopulation and significantly decreased granulocyte subpopulation. It is the first report suggesting an important role of AQP in the development and maturation of imrnunocytes.
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
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.
We reported the expression and function of aquaglyceroporin AQP3 in mouse peripheral nervous system.AQP3 mRNA was identified in freshly isolated mouse sciatic nerve by RT-PCR.Immunofluorescence using AQP3 antibody localized the protein expression in the myelin sheathe of sciatic nerve fibers.Although primary morpholo-gical evaluation of sciatic nerves from AQP3-knockout and wildtype mice revealed no significant difference,biochemical analysis demonstrated remarkably decreased glycerol and ATP contents in freshly isolated AQP3-knockout sciatic nerve.The study indicates an important role of facilitated glycerol transport mechanism in peripheral nerve energy metabolism.