• International Journal of Oral Biology
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• v.42 no.3
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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.

• Journal of the Korea Organic Resources Recycling Association
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• v.5 no.1
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• pp.25-32
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• 1997

The effect of levulinic acid (LA) and biosynthetic precursors of ${\delta}$-aminolevulinic acid (ALA) on the production of extracellular ALA was examined for the cells of soil derived Rhodospirillum rubrum N-1 belonged to the genus Rhodospirillaceae. The extracellular yield of ALA was increased to 23 fold (45 mg/l) from the basal condition (Lascelles' medium without L-glutamate) by successive addition of LA at initial (10 mM) and mid-log stage (30 mM) of cell cultivation. In addition to initial/mid-log mutual supplementations of LA (10 mM/30 mM) and glutamate (30/30 mM), respectively, by means of alternative feeding 10 mM $C_4$-precursors at mid-log phase of culture the extracellular ALA content was reached to 75 mg/l (40 fold).

• BMB Reports
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• v.40 no.6
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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.