Conantokin-G antagonism of the NMDA receptor subtype expressed in cultured cerebellar granule cells.
Conantokins are peptide antagonists of the N-methyl-D-aspartate (NMDA) subclass of excitatory amino acid receptors. We compared conantokin-G and AP5 antagonism of NMDA receptor activity expressed in cultures of neonatal rat cerebellar granule cells, using the fluorescent calcium indicator dye fura-2. The results were consistent with the binding of two molecules of agonist (NMDA) for channel activation and one antagonist molecule (AP5) for inhibition. However, conantokin-G antagonism was more complex: the peptide inhibited only approximately 70% of the elevation of intracellular free calcium produced by NMDA. These results, when combined with previous ones [8], suggest that conantokin-G may have different affinities for, and functional effects on, different subtypes of NMDA receptor complexes expressed in the mammalian CNS.
Haack
J A
JA
Department of Biology, University of Utah, Salt Lake City 84112.
Parks
T N
TN
Olivera
B M
BM
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020916:Conotoxins; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D004594:Electrophysiology; D016257:Fura-2; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D020916:Conotoxins; D010456:Peptides, Cyclic; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; C055407:conotoxin GV; D016257:Fura-2