Zheng F, Hasuo H, Gallagher J P
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77555-1031, USA.
Neuropharmacology. 1995 Aug;34(8):905-17. doi: 10.1016/0028-3908(95)00047-a.
Metabotropic glutamate receptors (mGluRs) form a receptor family that consists of diverse receptor subtypes; now, numbering 8--exclusive of splice variants. (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) has been suggested to be a selective agonist for the mGluRs. We have recently reported that, in rat dorsolateral septal nucleus (DLSN) neurones, a 1S,3R-ACPD-preferring inward current (ACPDi) persists in pertussis toxin-treated rats. We now report that this ACPDi-current: (1) persists in DLSN neurones dialyzed with a stable analog of GTP, namely, GTP gamma S; (2) exhibits a negative slope region with inward rectification in its I-V relationship; (3) persists in neurones superfused with tetrodotoxin or low calcium solutions; (4) is dependent upon both sodium and calcium ions; and (5) is independent of a reduction in temperature. Furthermore, pharmacological data suggest that this current may be activated by a unique type of excitatory amino acid (EAA) receptor, i.e. a receptor which prefers "metabotropic" EAA agonists and is insensitive to AP5 or CNQX. Activation by ACPD of inward currents associated with a conductance increase have also been reported at cultured mouse cerebellar Purkinje neurones; in slices of rat hippocampal CA1 neurones and slice cultures of hippocampal CA3 neurones. We suggest that this ACPDi current may play an important role within the CNS in the induction of long-term potentiation and other neurological processes; processes attributed previously to currents associated with NMDA receptor activation.
代谢型谷氨酸受体（mGluRs）构成了一个由多种受体亚型组成的受体家族；目前，其亚型数量为8种（不包括剪接变体）。(1S,3R)-1-氨基环戊烷-1,3-二羧酸（1S,3R-ACPD）被认为是mGluRs的选择性激动剂。我们最近报道，在大鼠背外侧隔核（DLSN）神经元中，百日咳毒素处理的大鼠中持续存在一种偏好1S,3R-ACPD的内向电流（ACPDi）。我们现在报道这种ACPDi电流：（1）在用稳定的GTP类似物即GTPγS透析的DLSN神经元中持续存在；（2）在其I-V关系中表现出内向整流的负斜率区域；（3）在灌注河豚毒素或低钙溶液的神经元中持续存在；（4）依赖于钠离子和钙离子；（5）与温度降低无关。此外，药理学数据表明，这种电流可能由一种独特类型的兴奋性氨基酸（EAA）受体激活，即一种偏好“代谢型”EAA激动剂且对AP5或CNQX不敏感的受体。在培养的小鼠小脑浦肯野神经元、大鼠海马CA1神经元切片和海马CA3神经元切片培养物中，也报道了ACPD激活与电导增加相关的内向电流。我们认为这种ACPDi电流可能在中枢神经系统中诱导长时程增强和其他神经过程中发挥重要作用；这些过程以前归因于与NMDA受体激活相关的电流。
