Role of cyclic ADP-ribose in signal transduction in airway cells.

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We investigated the basic electrophysiological characteristics of airway cells including tracheal submucosal gland acinar cells and tracheal smooth muscle. In addition, some roles of newly identified calcium mobilizing second messenger cyclic ADP-ribose was studied in these cells. Main findings of this project were as follows.1. Airway glands secrete electrolytes through Ca^<2+> released intracellularly. Inositol 1,4,5-trisphosphate (IP_3) plays a crucial role in Cl^--secretion. However, even in the cells perfused with mAb to IP_3 receptor, ACh caused a Ca^<2+>-dependent K-current.2. Intrcellular injection of cADPR caused outward K-current in gland cells.3. Microsomal fraction derived from tracheal gland released Ca^<2+> in respond to cADPR.Microsomes desensitized with IP_3 also responded to cADPR suggesting a separated Ca^<2+>-store is involved in cADPR-associated Ca(2+) release.4. cADPR did not affect the K-channel activities in excised patches nor affected influx of outside Ca^<2+>.5. Using RT-PCR,CD38-mRNA was detected in gland cells but not in tracheal smooth muscle cells. These findings suggest an existence of cADPR-pathways in Ca^<2+>-mobilization in airway gland cells.