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mGluR‐evoked augmentation of receptor‐mediated cyclic AMP formation in neonatal and adult rat striatum
Author(s) -
Cartmell Jayne,
Schaffhauser Hervé,
Wichmann Jürgen,
Mutel Vincent
Publication year - 1997
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 - 10.1038/sj.bjp.0701266
Subject(s) - agonist , striatum , metabotropic glutamate receptor , metabotropic receptor , medicine , long term potentiation , endocrinology , glycine , microdialysis , biology , adenosine , chemistry , receptor , pharmacology , biochemistry , dopamine , amino acid
The effects of selective agonists at group I, II and III metabotropic glutamate receptors (mGluRs) on adenosine A 2 receptor‐mediated cyclic AMP formation were compared in cross‐chopped slices of adult and neonatal (8 days old) rat striatum, in the presence of 1 u ml −1 adenosine deaminase. The group II selective agonist, (2 S ,1 R ,2 R ,3 R )‐2‐(2,3‐dicarboxycyclopropyl)glycine (DCG‐IV), elicited a potentiation of 5′‐N‐ethylcarboxamidoadenosine (NECA)‐stimulated cyclic AMP production with similar potencies in adult (EC 50 value 122±35 n M ) and neonatal (EC 50 value 285±6 n M ) brain. In contrast, the group I selective agonist ( S )‐dihydroxyphenylglycine (( S )‐DHPG) augmented the NECA cyclic AMP response in neonatal striatum (EC 50 value 9±1 μ M ), but at a concentration of 100 μ M , ( S )‐DHPG failed to affect the NECA response in adult striatal slices. The potentiation evoked by ( S )‐DHPG was specific for group I mGluRs as (2 S ,3 S ,4 S ,)‐2‐methyl‐2‐(carboxycyclopropyl)glycine (MCCG), a group II antagonist, was ineffective on the ( S )‐DHPG (100 μ M ) response at a concentration (500 μ M ) which reversed a similar augmentation elicited by DCG‐IV (300 n M ). Furthermore, a protein kinase C inhibitor (Ro 31‐8220, 10 μ M ) markedly reversed the effect of ( S )‐DHPG without affecting the response to DCG‐IV. The mGluR agonist (2 S ,3 S ,4 S ,)‐α‐(carboxycyclopropyl)glycine (L‐CCG‐I), elicited a greater potentiation of NECA‐stimulated cyclic AMP production in neonatal striatum in comparison with that observed in adult rat brain. Moreover, EC 50 values obtained from adult and neonatal striatum were 2±1 μ M and 9±1 μ M , respectively. These differences in potency might reflect co‐activation of both group I and group II mGluRs by L‐CCG‐I in neonatal striatum. Distinct patterns of mGluR expression in various brain areas might account for previous conflicting data on the nature of the mGluR able to evoke such potentiated responses.