Noble E P, Sincini E, Bergmann D, ten Bruggencate G
Alcohol Research Center, University of California, Los Angeles 90024.
Life Sci. 1989;44(1):19-26. doi: 10.1016/0024-3205(89)90213-0.
In rat prefrontal cortical slices, the excitatory amino acids N-methyl-D-aspartate (NMDA), ibotenate, L-aspartate, quisqualate, kainate and L-glutamate inhibit carbachol-induced phosphoinositide hydrolysis as measured by the accumulation of [3H]inositol-1-phosphate ([3H]IP1). NMDA dose-dependently inhibited the carbachol response (IC50 = 14.4 microM), and this inhibition was blocked by the NMDA receptor antagonist D,L-aminophosphonovaleric acid. Lowering medium Na+ concentration to 10 mM or exposing slices to pertussis toxin alleviated the inhibitory effect of NMDA on carbachol-induced [3H]IP1 formation. Serotonin-induced stimulation of [3H]IP1 was also inhibited by NMDA; in contrast, stimulation by norepinephrine, epinephrine or dopamine was unaffected. The results suggest that excitatory amino acids, besides their traditional role as stimulatory substances, can also act to inhibit the production of 2nd messengers activated by certain neurotransmitters in the brain.
在大鼠前额叶皮质切片中，兴奋性氨基酸N-甲基-D-天冬氨酸（NMDA）、鹅膏蕈氨酸、L-天冬氨酸、quisqualate、海人藻酸和L-谷氨酸可抑制由卡巴胆碱诱导的磷酸肌醇水解，这一过程通过[3H]肌醇-1-磷酸（[3H]IP1）的积累来测定。NMDA呈剂量依赖性地抑制卡巴胆碱反应（IC50 = 14.4 microM），且这种抑制作用可被NMDA受体拮抗剂D,L-氨基磷酸戊酸阻断。将培养基中Na+浓度降至10 mM或使切片暴露于百日咳毒素可减轻NMDA对卡巴胆碱诱导的[3H]IP1形成的抑制作用。5-羟色胺诱导的[3H]IP1刺激也受到NMDA抑制；相比之下，去甲肾上腺素、肾上腺素或多巴胺诱导的刺激则不受影响。结果表明，兴奋性氨基酸除了具有作为刺激物质的传统作用外，还可抑制大脑中某些神经递质激活的第二信使的产生。
