| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Outline of Final Research Achievements |
OGR1 family G-protein coupled receptors (GPCR), including OGR1, GPR4, and TDAG8, sense extracellular pH of 8.0-6.0, resulting in the activation of intracellular signaling pathways. Extracellular acidic pH of 6.8-6.1 has been shown to take place with ischemia and neurodegenerative. However, the mechanisms underlying acidic pH-induced actions are poorly understood. This study has especially focused on the roles of proton-sensing GPCR in mouse microglia and neuronal cells in acidic pH cultured medium. Our results suggested that acidic pH inhibits lipopolysaccaride-induced IL-1β production through the TDAG8/cAMP pathway in microglia, and stimulates neuronal NO synthase-mediated cGMP accumulation via OGR1/Ca2+ pathway in N1E115 cells. Thus, the elucidation of the molecular targets for acidic pH actions may provide therapeutic targets of neurodegenerative disorders such as ischemic stroke.
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