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

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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, 2′R, 3′R)-2-(2′, 3′-dicarboxycyclopropyl)glycine(DCG-IV) ≅ (2S, 1′S, 2′S)-2-(carboxycyclopropyl)glycine (L-CCG-I) > L-glutamate ≅ 2R, 4R-4-aminopyrrolidine-2, 4-dicarboxylate [(2R, 4R)-APDC] > (S)-4-carboxy-3-hydroxyphenylglycine [(S)-4C3HPG] ≅ 1S, 3R-1-aminocyclopentane-1, 3-dicarboxylate [(1S, 3R)-ACPD] > (S)-3-carboxy-4-hydroxyphenylglycine [(S)-3C4HPG] ≅ ibotenate. The negative logarithmically transformed EC<SUB>50</SUB>(pEC<SUB>50</SUB>) 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 G<SUB>i</SUB> proteins associated with adenylyl cyclase inhibition through group II mGluRs, in particular the mGluR2 subtype, in rat hippocampal and striatal membranes.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 84(4), 399-404, 2000-12-01

    The Japanese Pharmacological Society

References:  35

Codes

  • NII Article ID (NAID)
    10008186592
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    5611987
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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