Elsevier

Neuropharmacology

Volume 36, Issue 7, July 1997, Pages 933-940
Neuropharmacology

Pharmacological characterization of metabotropic glutamate receptors linked to the inhibition of adenylate cyclase activity in rat striatal slices

https://doi.org/10.1016/S0028-3908(97)00079-8Get rights and content

Abstract

The pharmacological profile of mGlu receptors negatively linked to adenylyl cyclase was characterized in adult rat striatal slices. Among the mGlu agonists tested, (+)-2-aminobicyclo[3.1.0]hexane-2, 6-dicarboxylate (LY354740), was the most potent inhibitor of forskolin-stimulated cAMP formation (EC50 = 11 ± 2nM). Inhibition of forskolin stimulation by the group III agonist L-2-amino-4-phosphono butanoate (L-AP4) was biphasic, the two parts of the concentration curve having EC50 values of 6 ± 1μM and 260 ± 4μM, suggesting a sequential recruitment of mGlu48 and mGlu7. The effects of several new phenylglycine derivative antagonists were tested on the inhibition of forskolin cAMP response by (2S, 1′S,2′S)-2-(carboxycyclopropyl)glycine (L-CCG I) and l-AP4. At 500 μM, (RS)-α-methyl-3-carboxy-methyl-phenylglycine was unable to antagonize the effect of l-CCG I or l-AP4 but (S)-α-methyl-3-carboxy-phenylalanine inhibited the effect of l-AP4 with a low potency. Finally, (RS)-α-methyl-4-tetrazolylphenylglycine and particularly (RS)-α-methyl-4-phosphonophenylglycine, appeared to be the most potent and selective antagonists of l-AP4 induced inhibition of forskolin-stimulated cAMP production in adult rat striatal slices.

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