• International Journal of Oral Biology
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• 제42권3호
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• pp.129-135
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• 2017

The present study investigated the role of spinal glutamate recycling in the development of orofacial inflammatory pain or trigeminal neuropathic pain. Experiments were carried out on male Sprague-Dawley rats weighing between 230 and 280 g. Under anesthesia, a polyethylene tube was implanted in the atlanto-occipital membrane for intracisternal administration. IL-$1{\beta}$-induced inflammation was employed as an orofacial acute inflammatory pain model. IL-$1{\beta}$ (10 ng) was injected subcutaneously into one vibrissal pad. We used the trigeminal neuropathic pain animal model produced by chronic constriction injury of the infraorbital nerve. DL-threo-${\beta}$-benzyloxyaspartate (TBOA) or methionine sulfoximine (MSO) was administered intracisternally to block the spinal glutamate transporter and the glutamine synthetase activity in astroglia. Intracisternal administration of TBOA produced mechanical allodynia in naïve rats, but it significantly attenuated mechanical allodynia in rats with interleukin (IL)-$1{\beta}$-induced inflammatory pain or trigeminal neuropathic pain. In contrast, intracisternal injection of MSO produced anti-allodynic effects in rats treated with IL-$1{\beta}$ or with infraorbital nerve injury. Intracisternal administration of MSO did not produce mechanical allodynia in naive rats. These results suggest that blockade of glutamate recycling induced pro-nociception in na?ve rats, but it paradoxically resulted in anti-nociception in rats experiencing inflammatory or neuropathic pain. Moreover, blockade of glutamate reuptake could represent a new therapeutic target for the treatment of chronic pain conditions.

• 유기물자원화
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• 제5권1호
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• pp.25-32
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• 1997

토양에서 분리한 광합성 세균인 Rhodospirillum rubrum N-1 균주에 의한 ${\delta}$-aminolevulinic acid (ALA) 생산에 있어서 levulinic acid (LA) 및 ALA 생합성 경로의 첨가효과를 검토하였다. Glutamate를 제외한 Lascelles의 기본배지에 LA를 배양초기에 10mM, 이후 대수기 중기에 30 mM을 첨가한 결과 균체외의 ALA 생산성은 최고 45 mg/l 도달, LA 미첨가 대비 23배 증가하였다. ALA 생합성의 전구물질인 glycine-succinate ($C_4$) 및 glutamate ($C_5$)의 feeding 효과는 배양초기/대수기 중기에 LA 10/30 mM을, glutamate 30 mM/30 mM을 각각 첨가하는 한편, 대수기 중기에 10 mM 농도의 $C_4$ 전구물질을 별도로 첨가배양함으로써 미첨가 대비의 ALA 생산성이 약 40배 (75 mg/l) 증가하였다.

• BMB Reports
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• 제40권6호
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• pp.1077-1082
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• 2007

Human glutamate dehydrogenase exists in hGDH1 (housekeeping isozyme) and in hGDH2 (nerve-specific isozyme), which differ markedly in their allosteric regulation. In the nervous system, GDH is enriched in astrocytes and is important for recycling glutamate, a major excitatory neurotransmitter during neurotransmission. Chloroquine has been known to be a potent inhibitor of house-keeping GDH1 in permeabilized liver and kidneycortex of rabbit. However, the effects of chloroquine on nerve-specific GDH2 have not been reported yet. In the present study, we have investigated the effects of chloroquine on hGDH2 at various conditions and showed that chloroquine could inhibit the activity of hGDH2 at dose-dependent manner. Studies of the chloroquine inhibition on enzyme activity revealed that hGDH2 was relatively less sensitive to chloroquine inhibition than house-keeping hGDH1. Incubation of hGDH2 was uncompetitive with respect of NADH and non-competitive with respect of 2-oxoglutarate. The inhibitory effect of chloroquine on hGDH2 was abolished, although in part, by the presence of ADP and L-leucine, whereas GTP did not change the sensitivity to chloroquine inhibition. Our results show a possibility that chloroquine may be used in regulating GDH activity and subsequently glutamate concentration in the central nervous system.