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NMDA channel activation regulates Ca 2+ permeation and gene transcription during histamine‐stimulated gastric acid secretion (904.5)
Author(s) -
Seo Ji Hye,
Itagaki Kiyoshi,
Wang Yaoyu,
Hagen Susan
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.904.5
Subject(s) - histamine , nmda receptor , creb , microbiology and biotechnology , biology , histamine h1 receptor , histamine h3 receptor , intracellular , chemistry , medicine , endocrinology , transcription factor , receptor , biochemistry , gene , agonist , antagonist
Background : Histamine‐stimulated gastric acid secretion is accompanied by oscillations in intracellular Ca 2+ . The receptor mediating these oscillations and the function of this Ca 2+ signal are unknown. We aimed to test the hypothesis that histamine stimulation activates N ‐methyl‐D‐aspartate (NMDA) channel‐mediated Ca 2+ influx and gene transcription in parietal cells. Methods : Cultured rat parietal cells were stimulated with histamine plus IBMX with or without NMDA channel antagonists. Intracellular Ca 2+ was visualized by microscopy using fura‐2 or fluo‐3. Western blots and RNA‐Seq were used to evaluate CREB/ATF‐1 activation and gene transcription, respectively. Results : Histamine stimulation induced Ca 2+ oscillations/permeation that were blocked by NMDA channel antagonists. CREB and ATF‐1 were activated by histamine stimulation and blocked by NMDA channel antagonists. Transcriptome analysis identified numerous up‐ and down‐regulated genes linked to histamine stimulation with a subset affected by NMDA channel blockade. The top network function attributed to NMDA channel‐mediated genes was cell death and survival. Most of the highly up‐regulated genes were CREB target genes. Conclusions: Histamine‐stimulated Ca 2+ oscillations are regulated by NMDA channels. Our data show that this pool of intracellular Ca 2+ transcriptionally regulates cell survival‐associated genes in parietal cells.