Point mutation increases a form of the NK_1 receptor with high affinity for neurokinin A and B and septide

摘要

The binding modalities of substance P and neurokinin A on the wild type and Gly~166 to-Cys mutant NK_1 receptors expressed on CHO cells were investigated in homologous and heterologous binding Experiments using both radiolabelled substance P and neurokinin A. On the wild type NK_1 receptor NKA displaces radiolabelled substance P with very low apparent Affinity, despite its high-affinity binding constant(determined in homologous binding experiments). The Gly~166 to -Cys substitution in the NK_1 tachykinin receptor greatly enhances the apparent affinity of Neurokinin A in competition for radiolabelled substance P, but it does not change the binding constant Of neurokinin A. The mutation, thereby, eliminates the discrepancy between the low apparent affinity And the high binding constant of neurokinin A.