Premium
Characterization of metabotropic glutamate receptor‐stimulated phosphoinositide hydrolysis in rat cultured cerebellar granule cells
Author(s) -
Toms N.J.,
Jane D.E.,
Tse HW.,
Roberts P.J.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb15932.x
Subject(s) - quisqualic acid , metabotropic glutamate receptor 1 , metabotropic glutamate receptor , glutamate receptor , metabotropic receptor , biology , inositol phosphate , biochemistry , metabotropic glutamate receptor 6 , cerebellum , metabotropic glutamate receptor 5 , agonist , granule cell , excitatory postsynaptic potential , chemistry , receptor , kainic acid , inositol , endocrinology , central nervous system , dentate gyrus
1 The pharmacology of excitatory amino acid (EAA)‐stimulated phosphoinositide (PI) hydrolysis, monitored via [ 3 H]‐inositol monophosphate accumulation, was investigated in primary cultures of rat cerebellar granule cells. 2 EAA‐stimulated PI hydrolysis peaked after 4–5 days in vitro and subsequently declined. 3 The agonist order of potency was found to be (EC 50 ): L‐quisqualic acid (Quis) (2 μ m )»L‐glutamate (50 μ m )>(1S,3R)‐11‐aminocyclopentane‐1,3‐dicarboxylic acid ((1S,3R)‐ACPD) (102 μ m ). L‐Glutamate (E max = 873% of basal activity) elicited the largest stimulation of PI hydrolysis, whereas Quis (E max = 603%) and (1S,3R)‐ACPD (E max = 306%) produced somewhat lower stimulations. 4 Several phenylglycine derivatives were found to be active in inhibiting 2 μ m Quis‐stimulated PI hydrolysis, in order of potency (IC 50 ): (S)‐4‐carboxy‐3‐hydroxyphenylglycine (41 μ m ) ≤ (S)‐4‐carboxyphenylglycine (51 μ m )»(+)‐α‐methyl‐4‐carboxyphenylglycine (243 μ m ). 5 Cultured cerebellar granule cells of the rat appear to have Group I mGluR pharmacology similar to that reported for cloned mGluRl and provide an ideal system for investigating novel mGluRl ligands in a native environment.