Shifting Receptor Sensitivities

AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors mediate excitatory responses to neurotransmitters in the brain and in other neurons of the central nervous system. Menuz et al . report that the presence or absence of auxiliary AMPA receptor subunits has a dramatic effect on the pharmacological properties of these receptors. The compound CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) generally acts as a competitive antagonist of AMPA receptors. However, in receptor complexes in which one of the auxiliary subunits known as TARPS (for transmembrane AMPA receptor regulatory proteins) is present, CNQX actually functions as a partial agonist of the receptor. The presence of the extra subunit may help couple conformational changes in the receptor ligand-binding domains to opening of the receptor ion channel. K. Menuz, R. M. Stroud, R. A. Nicoll, F. A. Hays, TARP auxiliary subunits switch AMPA receptor antagonists into partial agonists. Science 318 , 815-817 (2007). [Abstract] [Full Text]