Zheng F, Gallagher J P
Department of Pharmacology & Toxicology, University of Texas Medical Branch, Galveston 77555-1031, USA.
Neuroscience. 1995 Sep;68(2):423-34. doi: 10.1016/0306-4522(95)00128-6.
We have reported previously that a selective metabotropic glutamate receptor agonist, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), caused two primary postsynaptic membrane changes, namely, a slow membrane depolarization, and burst firing in rat dorsolateral septal nucleus neurons. In addition, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid also potentiates a slow after depolarization in rat dorsolateral septal nucleus neurons. We now report that, among all the postsynaptic membrane changes induced by (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid, only the burst firing was selectively blocked by pertussis toxin pretreatment. Thus, aminocyclopentane-1,3-dicarboxylic acid induced burst firing was mediated by a metabotropic receptor coupled to a pertussis toxin-sensitive GTP-binding protein, while the other induced cellular responses may be mediated by metabotropic glutamate receptors insensitive to pertussis toxin. We further characterized this receptor pharmacologically. This metabotropic receptor is activated by several metabotropic glutamate receptor agonists, but is insensitive to L-glutamate or L-aspartate. On the basis of its agonist activity profile, particularly the ineffectiveness of glutamate as an agonist, we have tentatively assigned the name aminocyclopentane-1,3-dicarboxylic acid metabotropic receptor, to this native, pertussis toxin-sensitive metabotropic receptor in the dorsolateral septal nucleus. Furthermore, this receptor is coupled to protein kinase C, probably via a phospholipase C independent pathway.
我们之前报道过，一种选择性代谢型谷氨酸受体激动剂，(1S,3R)-1-氨基环戊烷-1,3-二羧酸（1S,3R-ACPD），可引起大鼠背外侧隔核神经元突触后膜发生两种主要变化，即缓慢的膜去极化和爆发式放电。此外，(1S,3R)-1-氨基环戊烷-1,3-二羧酸还可增强大鼠背外侧隔核神经元的缓慢后去极化。我们现在报道，在(1S,3R)-1-氨基环戊烷-1,3-二羧酸诱导的所有突触后膜变化中，只有爆发式放电可被百日咳毒素预处理选择性阻断。因此，氨基环戊烷-1,3-二羧酸诱导的爆发式放电是由与百日咳毒素敏感的GTP结合蛋白偶联的代谢型受体介导的，而其他诱导的细胞反应可能由对百日咳毒素不敏感的代谢型谷氨酸受体介导。我们进一步从药理学角度对该受体进行了表征。这种代谢型受体可被几种代谢型谷氨酸受体激动剂激活，但对L-谷氨酸或L-天冬氨酸不敏感。根据其激动剂活性谱，特别是谷氨酸作为激动剂无效这一情况，我们初步将背外侧隔核中这种天然的、对百日咳毒素敏感的代谢型受体命名为氨基环戊烷-1,3-二羧酸代谢型受体。此外，该受体可能通过一条不依赖磷脂酶C的途径与蛋白激酶C偶联。
