Identification of 2-amino-2-methyl-4-phosphonobutanoic acid as an antagonist at the mGlu4a receptor

Abstract

2-Amino-2-methyl-4-phosphonobutanoic acid (MAP4) was tested for interactions with the mGlu_4a receptor which when expressed in baby hamster kidney (BHK570) cells couples to inhibition of forskolin-stimulated cAMP production. MAP4 had no agonist activity at this receptor and caused a concentration-dependent inhibition of the reduction in forskolin-stimulated cyclic AMP formation elicited by L-2-amino-4-phosphonobutanoic acid (L-AP4). Inhibition by MAP4 was consistent with a competitive mechanism of action (Schild slope = 1.2) with a K_i of 190 μM. MAP4 is the first antagonist identified for the mGlu_4a receptor.