Thio L L, Clifford D B, Zorumski C F
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110.
Neuroscience. 1993 Jan;52(1):35-44. doi: 10.1016/0306-4522(93)90179-j.
Previous experiments with wheatgerm agglutinin, an inhibitor of ionotropic quisqualate receptor desensitization, suggest that desensitization regulates quisqualate receptor-mediated synaptic transmission and excitotoxicity. Using whole-cell recordings from cultured postnatal rat hippocampal neurons, we have examined the wheatgerm agglutinin effect in further detail and compared it to other lectins. Wheatgerm agglutinin and other lectins belonging to the glucose/mannose, N-acetylglucosamine, and sialic acid classes inhibited desensitization. However, wheatgerm agglutinin was the most effective and had the most rapid onset of action. The inhibition was dose-dependent, and it was reduced and reversed by N-acetylglucosamine and N-acetylneuraminic acid. Treating neurons with neuraminidase, which cleaves sialic acid residues from the surface of cells, also diminished the effect. These results suggest that wheatgerm agglutinin reversibly inhibits ionotropic quisqualate receptor desensitization by interacting with carbohydrate residues on or near the quisqualate receptor complex. Future studies using the lectins may help to clarify the functional role of carbohydrate chains on the ionotropic quisqualate receptor.
此前使用麦胚凝集素(一种离子型quisqualate受体脱敏抑制剂)进行的实验表明,脱敏作用调节着quisqualate受体介导的突触传递和兴奋性毒性。利用原代培养的新生大鼠海马神经元进行全细胞记录,我们进一步详细研究了麦胚凝集素的作用,并将其与其他凝集素进行了比较。麦胚凝集素以及其他属于葡萄糖/甘露糖、N - 乙酰葡糖胺和唾液酸类别的凝集素均能抑制脱敏作用。然而,麦胚凝集素最为有效,且起效最为迅速。这种抑制作用呈剂量依赖性,并且可被N - 乙酰葡糖胺和N - 乙酰神经氨酸减弱及逆转。用神经氨酸酶处理神经元(该酶可从细胞表面切割唾液酸残基)也会减弱这种作用。这些结果表明,麦胚凝集素通过与quisqualate受体复合物上或其附近的碳水化合物残基相互作用,可逆性地抑制离子型quisqualate受体的脱敏作用。未来使用这些凝集素开展的研究可能有助于阐明离子型quisqualate受体上碳水化合物链的功能作用。