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机构地区:[1]中国科学技术大学生命科学学院神经生物学与生物物理学系,合肥230027 [2]第四军医大学基础部解剖学教研室,梁銶锯脑研究中心西安710032
出 处:《生理学报》1999年第4期361-370,共10页Acta Physiologica Sinica
基 金:国家自然科学基金
摘 要:采用制霉菌素穿孔膜片箝技术, 研究了P物质(substance P,SP) 对急性分离的大鼠骶髓后连合核神经元士的宁敏感性甘氨酸(glycine ,Gly) 反应的调控作用。在箝制电压为- 40 mV时,SP在1 nmol/L~1 μmol/L之间呈浓度依赖性地增强30 μmol/L甘氨酸激活的氯电流。SP既不改变IGly 的翻转电位, 也不影响Gly 与其受体的亲和力。Spantide 和选择性NK1 受体拮抗剂,L668 ,169 , 可阻断SP的增强作用, 而选择性NK2 受体拮抗剂,L659 ,877 则不能阻断SP对IGly 的增强作用, 提示SP对IGly 的增强作用是由NK1 受体介导的。在不同的神经元上,chelerythrine 或KN62 可去除SP对IGly 的增强作用, 提示蛋白激酶C或钙离子/ 钙调素依赖性的蛋白激酶Ⅱ可能参与了SP对IGly 增强作用的胞内机制。以上结果提示,SP可能通过增强Gly 的反应而抑制脊髓伤害性信息的传导。The modulatory effect of substance P (SP) on strychnine sensitive glycine (Gly) response was examined in neurons acutely dissociated from the rat sacral dorsal commissural nucleus (SDCN) using nystatin perforated patch recording configuration under voltage clamp conditions. Application of SP potentiated 30 μmol/L Gly activated chloride current ( I Gly ) in a concentration dependent manner over the range of 1 nmol/L to 1 μmol/L at a holding potential of -40 mV. SP neither changed the reversal potential of Gly response nor affected the affinity of Gly to its receptor. The SP potentiation effect could be blocked by spantide as well as a selective NK 1 receptor antagonist, L 668,169, but not by NK 2 receptor antagonist, L 659,877. The facilitatory action of SP on I Gly could also be abolished by pretreatment with chelerythrine or KN 62 in different neurons, a finding suggesting that protein kinase C (PKC) or Ca 2+ /calmodulin dependent protein kinase Ⅱ (CaMKⅡ) possibly contributes to an intracellular pathway of SP in the augmentation of I Gly . The results imply that SP may suppress nociception in the spinal cord by potentiating Gly response.
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