McDonald J W, Johnston M V
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.
Neurosci Lett. 1992 Oct 12;145(2):213-6. doi: 10.1016/0304-3940(92)90025-3.
The neuroprotective characteristics of the functional antagonist of metabotropic stimulated phosphoinositide hydrolysis, 2-amino-3-phosphonoproprionate (D,L-AP3), were examined alone and in combination with the non-competitive N-methyl-D-aspartate (NMDA) antagonist, MK-801, against ibotenate induced brain injury. Postnatal day (PND) 7 rats received unilateral stereotaxic intrastriatal injections of 10 nmol ibotenate and treated with either D,L-AP3 (600 nmol i.c.), MK-801 (1 mg/kg i.p.) or both. The severity of brain injury was assessed on PND 12 by comparison of the weights of injected and contralateral cerebral hemispheres. Ibotenate induced injury was partially reduced by treatment with MK-801 (34.0 +/- 4.4% protection, P < 0.05 vs. PBS treated, independent t-test) but not D,L-AP3. However, combined treatment with both MK-801 and D,L-AP3 produced marked synergistic neuroprotection (83.5 +/- 7.6% protection, P < 0.001 vs. PBS treated, independent t-test). The data suggest that metabotropic stimulated phosphoinositide hydrolysis contributes to excitotoxic neuronal injury in the presence of concurrent ionotropic receptor activation.
对促代谢型刺激磷酸肌醇水解的功能性拮抗剂2-氨基-3-膦酰丙酸（D，L-AP3）单独以及与非竞争性N-甲基-D-天冬氨酸（NMDA）拮抗剂MK-801联合使用时对鹅膏蕈氨酸诱导的脑损伤的神经保护特性进行了研究。出生后第7天（PND 7）的大鼠接受单侧立体定位纹状体内注射10 nmol鹅膏蕈氨酸，并分别用D，L-AP3（脑室内注射600 nmol）、MK-801（腹腔注射1 mg/kg）或两者进行治疗。在PND 12时，通过比较注射侧和对侧大脑半球的重量来评估脑损伤的严重程度。MK-801治疗可部分减轻鹅膏蕈氨酸诱导的损伤（保护率为34.0±4.4%，与PBS处理组相比，P<0.05，独立t检验），但D，L-AP3无此作用。然而，MK-801和D，L-AP3联合治疗产生了显著的协同神经保护作用（保护率为83.5±7.6%，与PBS处理组相比，P<0.001，独立t检验）。数据表明，在离子型受体同时激活的情况下，促代谢型刺激磷酸肌醇水解会导致兴奋性毒性神经元损伤。
