Natural agonist enhancing bis‐His zinc‐site in transmembrane segment V of the tachykinin NK3 receptor

Open Access
Publisher Website
Google Scholar
Abstract
In the wild‐type tachykinin NK3A receptor histidyl residues are present at two positions in TM‐V, V:01 and V:05, at which Zn2+ functions as an antagonist in NK1 and κ‐opioid receptors with engineered metal‐ion sites. Surprisingly, in the NK3A receptor Zn2+ instead increased the binding of the agonist 125I‐[MePhe7]neurokinin B to 150%. [MePhe7]neurokinin B bound to the NK3A receptor in a two‐component mode of which Zn2+ eliminated the subnanomolar binding mode but induced a higher binding capacity of the nanomolar binding mode. Signal transduction was not induced by ZnCl2 but 10 μM ZnCl2 enhanced the effect of neurokinin B. Ala‐substitution of HisV:01 eliminated the enhancing effect of Zn2+ on peptide binding. It is concluded that physiological concentrations of Zn2+ have a positive modulatory effect on the binding and function of neurokinin B on the NK3A receptor through a bis‐His site in TM‐V.