title: Calcium regulates estrogen increase in permeability of cultured CaSki epithelium by eNOS-dependent mechanism.
abstract: Estrogen increases baseline transepithelial permeability across CaSki cultures and augments the increase in permeability in response to hypertonic gradients. In estrogen-treated cells, lowering cytosolic calcium abrogated the hypertonicity-induced augmented increase in permeability and decreased baseline permeability to a greater degree than in estrogen-deprived cells. Steady-state levels of cytosolic calcium in estrogen-deprived cells were higher than in estrogen-treated cells. Increases in extracellular calcium increased cytosolic calcium more in estrogen-deprived cells than in estrogen-treated cells. However, in estrogen-treated cells, increasing cytosolic calcium was associated with greater increases in permeability in response to hypertonic gradients than in estrogen-deprived cells. Lowering cytosolic calcium blocked the estrogen-induced increase in nitric oxide (NO) release and in the in vitro conversion of L-[(3)H]arginine to L-[(3)H]citrulline. Treatment with estrogen upregulated mRNA of the NO synthase isoform endothelial nitric oxide synthase (eNOS). These results indicate that cytosolic calcium mediates the responses to estrogen and suggest that the estrogen increase in permeability and the augmented increase in permeability in response to hypertonicity involve an increase in NO synthesis by upregulation of the calcium-dependent eNOS.
authors.affiliation: Departments of Reproductive Biology and Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA. gig@po.cwru.edu
authors.forename: G I
authors.initials: GI
authors.lastname: Gorodeski
mesh_terms: D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002461:Cell Line, Transformed; D002463:Cell Membrane Permeability / Q000502:physiology; D002584:Cervix Uteri / Q000166:cytology / Q000378:metabolism*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004553:Electric Conductivity; D004847:Epithelial Cells / Q000378:metabolism; D004967:Estrogens / Q000502:physiology*; D005260:Female; D006801:Humans; D006982:Hypertonic Solutions / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology
chemical_list: D004967:Estrogens; D006982:Hypertonic Solutions; D007476:Ionophores; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D015759:Ionomycin; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP; D002118:Calcium