Miller G W, Schnellmann R G
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens 30602-7389.
Life Sci. 1993;53(15):1203-9. doi: 10.1016/0024-3205(93)90538-e.
Previous studies have shown that the neuronal glycine receptor antagonist, strychnine, mimics the cytoprotective effects of glycine in renal proximal tubules (RPT) (1). The goal of this study was to identify and characterize the site of action of strychnine. 3H-Strychnine bound to RPT in a saturable and reversible manner, and was displaced by unlabelled strychnine (IC50 = 0.87 mM and a Bmax = 57 nmol/mg protein). However, strychnine binding was not inhibited by glycine or related cytoprotective amino acids. Furthermore, the neurotoxicants bicuculline and norharmane, which share the cytoprotective properties of strychnine, inhibited 3H-strychnine binding. These data support the existence of a novel low-affinity strychnine binding site on the RPT plasma membrane that prevents toxic cell death.
先前的研究表明，神经元甘氨酸受体拮抗剂士的宁可模拟甘氨酸在肾近端小管（RPT）中的细胞保护作用（1）。本研究的目的是确定并表征士的宁的作用位点。3H-士的宁以可饱和且可逆的方式与RPT结合，并被未标记的士的宁取代（IC50 = 0.87 mM，Bmax = 57 nmol/mg蛋白质）。然而，甘氨酸或相关的具有细胞保护作用的氨基酸并不抑制士的宁的结合。此外，具有士的宁细胞保护特性的神经毒物荷包牡丹碱和去甲哈尔满抑制了3H-士的宁结合。这些数据支持在RPT质膜上存在一个新的低亲和力士的宁结合位点，该位点可防止毒性细胞死亡。
