Delaney S M, Geiger J D
Department of Pharmacology and Therapeutics, University of Manitoba Faculty of Medicine, Winnipeg, Canada.
Brain Res. 1995 Dec 8;702(1-2):72-6. doi: 10.1016/0006-8993(95)01010-9.
Unilateral microinjection of N-methyl-D-aspartate (NMDA) into striatum of rats subsequently killed by high-energy focused microwave irradiation significantly increased in vivo levels of endogenous adenosine. At a dose of 25 nmol NMDA, levels of adenosine in injected striata were 263% of levels in uninjected contralateral striata. An inhibitor of adenosine deaminase (deoxycoformycin, DCF) in combination with an inhibitor of adenosine transport (dilazep, DLZP) at a dose that did not affect levels of endogenous adenosine, potentiated NMDA-induced increases in adenosine levels to 426% of contralateral striata. In the presence of DCF and DLZP, NMDA dose-dependently increased levels of adenosine (% of contralateral striatum) from 166% at 10 nmol to 622% at 100 nmol. NMDA-induced increases in levels of endogenous adenosine were completely blocked by prior administration of the NMDA receptor antagonist MK 801 (dizocilpine). Inhibitors of adenosine metabolism and transport may provide therapeutic benefit by potentiating excitatory amino acid-induced increases in levels of endogenous adenosine in vivo.
将 N-甲基-D-天冬氨酸（NMDA）单侧微量注射到随后被高能聚焦微波辐射处死的大鼠纹状体中，可显著提高体内内源性腺苷水平。在 25 nmol NMDA 的剂量下，注射侧纹状体中的腺苷水平是未注射的对侧纹状体中水平的 263%。一种腺苷脱氨酶抑制剂（脱氧助间型霉素，DCF）与一种腺苷转运抑制剂（地拉卓，DLZP）联合使用，其剂量不影响内源性腺苷水平，可将 NMDA 诱导的腺苷水平升高增强至对侧纹状体的 426%。在存在 DCF 和 DLZP 的情况下，NMDA 剂量依赖性地增加腺苷水平（相对于对侧纹状体的百分比），从 10 nmol 时的 166%增加到 100 nmol 时的 622%。NMDA 诱导的内源性腺苷水平升高被预先给予的 NMDA 受体拮抗剂 MK 801（地佐环平）完全阻断。腺苷代谢和转运抑制剂可能通过增强兴奋性氨基酸诱导的体内内源性腺苷水平升高而提供治疗益处。
