GDP beta S antagonizes whole-cell current responses to excitatory amino acids

Guanine nucleotides have been predicted to be NMDA antagonists in tissue binding studies. Using the patch-clamp technique, we now show that the guanine nucleotide GDP beta S produces a rapidly reversible antagonism of NMDA, kainate, and, less potently, quisqualate whole-cell current responses. Furthermore, it does not appear that this antagonism is effected intracellularly. Our results suggest a novel extracellular role for guanine nucleotides apart from their traditional intracellular actions on G-proteins.