演題番号 : P1-a31
小久保 宏俊 / Hirotoshi Kokubo:1 山森 早織 / Saori Yamamori:1 板倉 誠 / Makoto Itakura:1 飯田 諭宜 / Yuuki Iida:2 宮岡 等 / Hitoshi Miyaoka:2 高橋 正身 / Masami Takahashi:1,3
1:北里大学医学部生化学 / Department of Biochemistry Kitasato Universuty School of Medicine 2:北里大学医学部精神神経科学 / Deaprtment of Psychiatry Kitasato Universuty School of Medicine 3:CREST, JST
SNAP-25 plays essential role in neurotransmitter release by exocytosis as a t-SNARE protein. Previously, we showed that protein kinase C (PKC) phosphorylated SNAP-25 on Ser187 and enhanced neurotransmitter release from neurosectreory cells by recruiting secretory vesicles near to the plasma membrane. Recently, we showed that SNAP-25 was phosphorylated in mouse brain after exposure to cold restrained stress. In order to know the signal transduction system that regulates the phosphorylation of SNAP-25 in mouse brain, we examine the effect of various drugs on the stress-induced phosphorylation of SNAP-25. It is well established that monoamines such as noradrenaline, dopamine and serotonin, play important roles in the regulation and/or expression of stress response. Reserpine is a potent drug to exhaust brain monoamines by inhibiting vesicular monoamine transporters. Two days after reserpine administration, dopamine and serotonin contents in mouse brain were decreased to less than 3.5% of control mice. Surprisingly, reserpine elevated phosphorylation levels of SNAP-25 in hippocampus two days after the administration, and no significant further increase was observed by cold restrained stress, suggesting that the phosphorylation of SNAP-25 was negatively regulated by some kinds of monoamines. To verify this suggestion, we next examined the effect of an antagonist of monoamine receptors. Clozapine is an antipsychotic drug and has antagonistic effects on broad range of monoamine receptors including D1, D2, 5HT-2, H1, and α-1 receptors. The phosphorylation levels of SNAP-25 were increased in hippocampus as well as in cerebral cortex 120 min after clozapine administration, and no significant additional increase in SNAP-25 phosphorylation was induced by the stress exposure. These results rise a possibility that some monoamines regulate stress response through the inhibition of SNAP-25 phosphorylation in mouse brain.