Meller S T, Dykstra C, Gebhart G F
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City 52242.
Eur J Pharmacol. 1992 Apr 7;214(1):93-6. doi: 10.1016/0014-2999(92)90102-a.
The intrathecal (i.t.) administration of either N-methyl-D-aspartate (NMDA, 10 fmol to 10 pmol) or L-arginine (1 pmol to 10 nmol), but not D-arginine (1 pmol to 10 nmol), produced a rapid, transient, dose-dependent facilitation (maximal response of 30.9 +/- 6.0% and 33.7 +/- 1.5%, respectively) of the nociceptive tail-flick reflex (ED50 = 47.8 +/- 15.4 fmol and 11.4 +/- 2.7 pmol, respectively). Maximal NMDA-produced facilitation of the tail-flick reflex (1 pmol i.t.) was completely abolished by prior treatment (10 min prior) with either N omega-nitro-L-arginine methyl ester (L-NAME, 10 nmol i.t.), methylene blue (10 nmol i.t.) or DL-5-aminophosphonovaleric acid (AP5, 100 pmol i.t.). NMDA-produced facilitation was completely recovered 40 min after L-NAME, 50 min after methylene blue and 30 min after AP5. L-NAME, methylene blue or AP5 did not significantly alter baseline tail-flick latency. These results suggest that NMDA-produced facilitation of a thermal nociceptive reflex is mediated through activation of an NMDA receptor that results in an increase in endogenous nitric oxide and activation of soluble guanylate cyclase in lumbar spinal cord.
鞘内注射N-甲基-D-天冬氨酸（NMDA，10飞摩尔至10皮摩尔）或L-精氨酸（1皮摩尔至10纳摩尔），而非D-精氨酸（1皮摩尔至10纳摩尔），可快速、短暂、剂量依赖性地促进伤害性甩尾反射（最大反应分别为30.9±6.0%和33.7±1.5%）（ED50分别为47.8±15.4飞摩尔和11.4±2.7皮摩尔）。鞘内注射1皮摩尔NMDA对甩尾反射产生的最大促进作用，可被预先（提前10分钟）用Nω-硝基-L-精氨酸甲酯（L-NAME，鞘内注射10纳摩尔）、亚甲蓝（鞘内注射10纳摩尔）或DL-5-氨基膦酸戊酸（AP5，鞘内注射100皮摩尔）处理完全消除。L-NAME处理后40分钟、亚甲蓝处理后50分钟以及AP5处理后30分钟，NMDA产生的促进作用完全恢复。L-NAME、亚甲蓝或AP5并未显著改变基线甩尾潜伏期。这些结果表明，NMDA对热伤害性反射的促进作用是通过激活NMDA受体介导的，该受体导致内源性一氧化氮增加，并激活腰段脊髓中的可溶性鸟苷酸环化酶。
