Johnson K M, Sacaan A I, Snell L D
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.
Eur J Pharmacol. 1988 Jul 26;152(1-2):141-6. doi: 10.1016/0014-2999(88)90845-x.
It has been reported that glutamate can increase the binding of [3H]TCP to phencyclidine (PCP) receptors by an action on receptors which are selective for N-methyl-D-aspartate (NMDA). Recently this laboratory has reported that glycine and magnesium can amplify this effect of NMDA agonists in well-washed, lysed cortical membranes. Here we report that maximally effective concentrations of glutamate (10 microM), NMDA (300 microM), MgCl2 (300 microM) and glycine (10 microM) increase the affinity of the PCP receptor for [3H]TCP by approximately 4-fold in the absence of any change in the density of PCP receptors. However, in combination with glutamate, magnesium had the further effect of increasing the Bmax by about 75%. Finally, a synaptosomal P2 preparation, which had not been washed to minimize the concentration of endogenous effectors had a Bmax value similar to the well-washed preparation, but had a KD value 8-fold lower. These data indicate that the primary effect of NMDA agonists, glycine, and low concentrations of magnesium ions is to convert the PCP receptor from a low-affinity to a high-affinity state. These data are discussed in relation to the functional regulation of the NMDA ionophore.
据报道，谷氨酸可通过作用于对N-甲基-D-天冬氨酸（NMDA）具有选择性的受体，增加[3H]TCP与苯环己哌啶（PCP）受体的结合。最近，本实验室报道，甘氨酸和镁可在充分洗涤、裂解的皮质膜中放大NMDA激动剂的这种作用。在此我们报告，在PCP受体密度无任何变化的情况下，谷氨酸（10 microM）、NMDA（300 microM）、MgCl2（300 microM）和甘氨酸（10 microM）的最大有效浓度可使PCP受体对[3H]TCP的亲和力增加约4倍。然而，与谷氨酸联合使用时，镁还具有使Bmax增加约75%的进一步作用。最后，未经过洗涤以尽量减少内源性效应物浓度的突触体P2制剂，其Bmax值与充分洗涤的制剂相似，但KD值低8倍。这些数据表明，NMDA激动剂、甘氨酸和低浓度镁离子的主要作用是将PCP受体从低亲和力状态转变为高亲和力状态。本文结合NMDA离子通道的功能调节对这些数据进行了讨论。
