Premium
Differential Regulation of Intracellular Signaling Systems by Sodium Fluoride in Rat Glioma Cells
Author(s) -
Kagaya Ariyuki,
Uchitomi Yosuke,
Kugaya Akira,
Takebayashi Minoru,
Nagaoka Ikuo,
Muraoka Mitsutaro,
Yokota Norio,
Yamawaki Shigeto
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.66041483.x
Subject(s) - intracellular , sodium fluoride , glioma , fluoride , chemistry , microbiology and biotechnology , sodium , differential (mechanical device) , signal transduction , neuroscience , biology , cancer research , engineering , inorganic chemistry , organic chemistry , aerospace engineering
Abstract: We investigated the rapid and slow effects of NaF on intracellular signaling systems such as Ca 2+ homeostasis and cyclic GMP (cGMP) generation in rat glioma C6 cells, using the Ca 2+ ‐sensitive dye fura‐2 and cGMP enzyme immunoassay. We found that the following: (a) NaF enhanced cGMP generation in a concentration‐dependent manner. This enhancement was abolished by pretreatment with 100 µ M BAPTA tetraacetoxymethyl ester or in the presence of W‐7 in a concentration‐dependent manner. N G ‐Monomethyl‐ l ‐arginine (NMMA), a competitive inhibitor of nitric oxide synthase (NOS), also inhibited the NaF‐induced generation of cGMP. These results suggest that NaF‐induced cGMP generation occurs via a calcium/calmodulin‐ and NOS‐dependent pathway. (b) The basal intracellular Ca 2+ concentration ([Ca 2+ ] i ) was transiently greater at 1 and 3 h after pretreatment with NaF. W‐7 and W‐13 antagonized the increase in [Ca 2+ ] i , whereas NMMA had little effect. This suggests that the NaF‐induced change in basal [Ca 2+ ] i was mediated by a calmodulin‐dependent pathway but was independent of a NOS‐sensitive pathway. (c) The serotonin (5‐HT)‐induced intracellular mobilization of Ca 2+ was reduced by pretreating the cells with NaF. The reduction in Ca 2+ mobilization was antagonized by genistein, a tyrosine kinase inhibitor. W‐7, W‐5, and H‐8 had no effect. Results suggest that NaF differentially regulates the cGMP generation, basal [Ca 2+ ] i , and 5‐HT 2A receptor function in C6 glioma cells.