Pathways Signaling the Regulatory Volume Decrease of Cultured Nonpigmented Ciliary Epithelial Cells

摘要: Purpose. The authors identify the signaling pathways tor regulatory volume decrease (RVD) of nonpigmented ciliary epithelial (NPE) cells. RVD is a response triggered by swelling and reflecting K.C1 release NPE Methods. cell volumes human cells were measured in suspension electronic sorting. Measurements conducted test solutions constant ionic strength, but osmolality was varied sucrose. Results. Cyclic AMP (cAMP), forskolin, PGE2, PKC-inhibitor staurosporine, increasing cytoplasmic Ca' 2+ activity with thapsigargin all enhanced RVD. Leukotrienes A4, D4, E4, protein phosphatasc inhibitor okadaic acid had no detectable effect under current experimental conditions. cyclooxygenase indomelhacin, epoxygenase inhibitors ketoconazole SKF 525A, PKC activator DiCK downregulatcd addition cation ionophore, gramicidin, increased In presence cAMP, indomethacin did not affect RVD, ketoconazole, DiCK, calcium-calmodulin blocker trilluoroperazine still inhibited—and staurosporine enhanced—the Many these observations are strikingly different from results reported other Anisosinotic increase intraccllular cAMP concentration. Conclusions. responses to unique for each type. propose that hypotonic stimulates arachidonic turnover, triggering PGE^-mediated upregulation K + channels epoxide-mediatcd Cl~ channels. Swelling may also reduce endogenous activity, further upregulating Calcium-calmodulin plays permissive role CI" Invest Ophthalmol Vis Sci. 1994;35:2876-2886.