RESUMEN
N-methyl-D-aspartate receptors play an important role in nociceptive transmissions in various types of pain. In this study, we investigated the pain-related response in mice lacking the N-methyl-D-aspartate-type glutamate receptor epsilon1 or epsilon4 subunit in the formalin test and in the partial sciatic nerve ligation-induced neuropathic pain model. The second tonic inflammatory phase response in the formalin test was significantly reduced in glutamate receptor epsilon1 knockout epsilon1(-/-) mice, but not in glutamate receptor epsilon4(-/-) when compared with wild-type mice. In the partial sciatic nerve ligation model, glutamate receptor epsilon1(-/-) mice exhibited no difference in mechanical allodynia compared with wild-type mice. Glutamate receptor epsilon4(-/-) mice, however, failed to develop allodynia after the nerve ligation. These results suggest that glutamate receptor epsilon1 and epsilon4 subunits are involved in tonic inflammatory pain and neuropathic allodynia, respectively.
Asunto(s)
Inflamación/fisiopatología , Dolor/fisiopatología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Receptores de N-Metil-D-Aspartato/fisiología , Animales , Formaldehído , Inflamación/complicaciones , Ligadura , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Dolor/etiología , Dimensión del Dolor/efectos de los fármacos , Enfermedades del Sistema Nervioso Periférico/complicaciones , Estimulación Física , Receptores de N-Metil-D-Aspartato/genética , Neuropatía Ciática/fisiopatologíaRESUMEN
A new D-glucose-6-phosphate phosphohydrolase (G6Pase) inhibitor, CJ-21,164 (1) was isolated from the fermentation broth of the fungus Chloridium sp. CL48903. The structure was elucidated to be a novel tetramer of the salicylic acid derivatives by spectroscopic analyses. Compound I inhibited G6Pase in rat liver microsomes with an IC50 of 1.6 microM. Glucose output from hepatocytes isolated from rat liver was inhibited when I was present in the incubation medium, consistent with the role of I as a G6Pase inhibitor.
Asunto(s)
Benzoatos/aislamiento & purificación , Inhibidores Enzimáticos/aislamiento & purificación , Monoéster Fosfórico Hidrolasas/antagonistas & inhibidores , Animales , Benzoatos/química , Benzoatos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Fermentación , Glucosa/metabolismo , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/enzimología , Estructura Molecular , Ratas , Ratas Sprague-DawleyRESUMEN
A new equisetin derivative, CJ-21,058 (I) was isolated from the fermentation broth of an unidentified fungus CL47745. It shows antibacterial activity against Gram-positive multi-drug resistant bacteria by inhibiting ATP-dependent translocation of precursor proteins across a bacterial cell membrane.