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Metabotropic Glutamate Receptor in C6BU‐1 Glioma Cell Has NMDA Receptor‐Ion Channel Complex‐Like Properties and Interacts with Serotonin 2 Receptor‐Stimulated Signal Transduction
Author(s) -
Shinno Hideto,
Mikuni Masahiko,
Saitoh Kazuko,
Tomita Urara,
Yamawaki Shigeto,
Takahashi Kiyohisa
Publication year - 1994
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1994.63041346.x
Subject(s) - metabotropic glutamate receptor 1 , metabotropic glutamate receptor , metabotropic glutamate receptor 6 , metabotropic glutamate receptor 5 , metabotropic receptor , nmda receptor , pertussis toxin , metabotropic glutamate receptor 7 , glutamate receptor , metabotropic glutamate receptor 2 , chemistry , receptor , biology , microbiology and biotechnology , biochemistry , g protein
We found in cultured glioma (C6BU‐1) cells that excitatory amino acids (EAAs) such as glutamate, N ‐methyl‐ d ‐aspartate (NMDA), aspartate, and metabotropic glutamate receptor agonist trans ‐(±)‐1‐amino‐1,3‐cyclopentanedicarboxylate caused an increase in the inositol 1,4,5‐trisphosphate formation and the intracellular Ca 2+ concentration ([Ca 2+ ] i ) in the absence of extracellular Mg 2+ and Ca 2+ . Pertussis toxin treatment abolished this glutamate‐induced [Ca 2+ ] i increase. Various antagonists against NMDA receptor‐ion channel complex, such as Mg 2+ , d ‐2‐amino‐5‐phosphonovalerate ( d ‐APV), HA‐966, and MK‐801, also inhibited the increase in [Ca 2+ ] i induced by glutamate. These results indicate that these metabotropic EAA receptors coupled to pertussis toxin‐susceptible GTP‐binding protein and phospholipase C system in C6BU‐1 glioma cells have the pharmacological properties of NMDA receptor‐ion channel complexes. We also found that in the presence of Mg 2+ these metabotropic receptors resemble the NMDA receptor‐ion channel complex interacted with 5‐hydroxytryptamine 2 (5‐HT 2 ) receptor signaling. EAAs inhibited 5‐HT 2 receptor‐mediated intracellular Ca 2+ mobilization and inositol 1,4,5‐trisphosphate formation in a concentration‐dependent manner. The inhibitory effect of glutamate was reversed by various NMDA receptor antagonists ( d ‐APV, MK‐801, phencyclidine, and HA‐966), but l ‐APV failed to block the inhibitory effect of glutamate. The same result was observed in the absence of extracellular Ca 2+ . In addition, this inhibitory effect on 5‐HT 2 receptor‐mediated signal transduction was abolished by treatment of C6BU‐1 cells with pertussis toxin, whereas 5‐HT 2 receptor‐mediated [Ca 2+ ] i increase was not abolished by pertussis toxin treatment. We can, therefore, conclude that the inhibitory effect of glutamate is not a result of the influx of Ca 2+ through the ion channel and that it operates via metabotropic glutamate receptors, having NMDA receptor‐ion channel complex‐like properties and being coupled with pertussis toxin‐sensitive GTP‐binding protein and phospholipase C.