IDENTIFICATION OF 2-AMINO-2-METHYL-4-PHOSPHONOBUTANOIC ACID AS AN ANTAGONIST AT THE MGLU(4A) RECEPTOR

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 mu M. MAP4 is the first antagonist identified for the mGlu(4a) receptor.