Direct binding properties of conantokins to native N-methyl-d-aspartate receptors.

摘要: Conantokin-G (con-G) is a small, gamma-carboxyglutamic acid (Gla)-containing peptide that functions neurophysiologically by inhibiting the N-methyl-d-aspartate receptor (NMDAR). In current study, binding properties of an alanine-rich, Gla-deficient con-G variant, Ala-con-G, were assessed following tracer radioiodination with 125I. Direct experiments [125I]Ala-con-G yielded single site defined Kd value 516 +/- 120 nm. Displacement Ala-con-G resulted in 100% displacement IC50 564 33 nm, while heterologous con-G[S16Y], con-G, con-T, and con-R[1-17] values range 15-45 microm. No was observed d-gamma-con-G or con-G[L5A], analogs are inactive at NMDARs. Specific displaced NMDA 2-amino-5-phosphopentanoic dose-dependent manner, suggesting interaction glutamate site. The direct to adult rat brain sections revealed anatomical distribution sites all regions known contain NR2B subunit NMDAR. These results constitute only demonstration radiolabeled conantokin NMDARs present membrane preparations sections, suggest similar derivatives, may find utility as probes variety systems.