Identification of 2-amino-2-methyl-4-phosphonobutanoic acid as an antagonist at the mGlu4a receptor.
2-Amino-2-methyl-4-phosphonobutanoic acid (MAP4) was tested for interactions with the mGlu4a 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 Ki of 190 microM. MAP4 is the first antagonist identified for the mGlu4a receptor.
Johansen
P A
PA
Children's Seashore House, Children's Hospital of Philadelphia, PA 19104, USA.
Robinson
M B
MB
D000613:Aminobutyrates / Q000494:pharmacology*; D000818:Animals; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D007668:Kidney / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*
C089836:2-amino-2-methyl-4-phosphonobutyrate; D000613:Aminobutyrates; D018691:Excitatory Amino Acid Antagonists; D007473:Ion Channels; D018094:Receptors, Metabotropic Glutamate