Jpn. J. Pharmacol. 84 (4), 399-404 (2000)


Stimulation of High-Affinity GTPase Activity Through Group II Metabotropic Glutamate Receptors in Rat Hippocampal and Striatal Membranes

Yuji Odagaki*, Nobuyuki Nishi and Tsukasa Koyama

Department of Psychiatry, Hokkaido University Graduate School of Medicine, North 15, West 7, Sapporo 060-8638, Japan
*Corresponding author.
Present address for correspondence: Department of Psychiatry, Saitama Medical School, 38 Morohongo, Moroyama-cho Iruma-gun, Saitama 350-0495, Japan
FAX:+81-492-76-1622, E-mail: odagaki@saitama-med.ac.jp


Abstract: The stimulation of high-affinity GTPase activity through metabotropic glutamate receptors (mGluRs) was pharmacologically characterized with the use of a series of agonists for mGluRs in rat hippocampal and striatal membranes. The pharmacological profile of the response was almost identical to each other between both brain regions. Thus, the high-affinity GTPase activities were stimulated by several mGluR-related compounds with the following rank order of potency: (2S,2ĘR,3ĘR)-2-(2Ę,3Ę-dicarboxycyclopropyl)glycine (DCG-IV)&nbsp Š=Š  (2S,1ĘS,2ĘS)-2-(carboxycyclopropyl)glycine (L-CCG-I)  > L-glutamate&nbsp Š=Š  2R,4R-4-aminopyrrolidine-2,4-dicarboxylate [(2R,4R)-APDC]  > (S)-4-carboxy-3-hydroxyphenylglycine [(S)-4C3HPG]&nbsp Š=Š  1S,3R-1-aminocyclopentane-1,3-dicarboxylate [(1S,3R)-ACPD]  > (S)-3-carboxy-4-hydroxyphenylglycine [(S)-3C4HPG]&nbsp Š=Š  ibotenate. The negative logarithmically transformed EC50 (pEC50) values of these compounds in both brain regions were significantly correlated with those reported previously in the cerebral cortical membranes (N. Nishi et al., Br. J. Pharmacol., 130, 1664-1670, 2000). On the contrary, other reagents including a selective group I mGluRs agonist, (RS)-3,5-dihydroxyphenylglycine [(RS)-3,5-DHPG], and selective group III mGluRs agonists such as L(+)-2-amino-4-phosphonobutylate (L-AP4) and L-serine-O-phosphate (L-SOP) had little or no effects even at the highest concentration examined. Quisqualate was also a very weak agonist in both regions. These results indicate that mGluR-mediated high-affinity GTPase activity derives from the Gi proteins associated with adenylyl cyclase inhibition through group II mGluRs, in particular the mGluR2 subtype, in rat hippocampal and striatal membranes.

Keywords: Metabotropic glutamate receptor, G protein, High-affinity GTPase, Hippocampus, Striatum


Copyright© The Japanese Pharmacological Society 2000

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