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Natural agonist enhancing bis‐His zinc‐site in transmembrane segment V of the tachykinin NK 3 receptor
Author(s) -
Rosenkilde Mette M,
Lucibello Maria,
Holst Birgitte,
Schwartz Thue W
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)01331-3
Subject(s) - agonist , chemistry , tachykinin receptor , zinc , receptor , transmembrane protein , pharmacology , biology , biochemistry , substance p , organic chemistry , neuropeptide
In the wild‐type tachykinin NK 3A receptor histidyl residues are present at two positions in TM‐V, V:01 and V:05, at which Zn 2+ functions as an antagonist in NK 1 and κ‐opioid receptors with engineered metal‐ion sites. Surprisingly, in the NK 3A receptor Zn 2+ instead increased the binding of the agonist 125 I‐[MePhe 7 ]neurokinin B to 150%. [MePhe 7 ]neurokinin B bound to the NK 3A receptor in a two‐component mode of which Zn 2+ eliminated the subnanomolar binding mode but induced a higher binding capacity of the nanomolar binding mode. Signal transduction was not induced by ZnCl 2 but 10 μM ZnCl 2 enhanced the effect of neurokinin B. Ala‐substitution of HisV:01 eliminated the enhancing effect of Zn 2+ on peptide binding. It is concluded that physiological concentrations of Zn 2+ have a positive modulatory effect on the binding and function of neurokinin B on the NK 3A receptor through a bis‐His site in TM‐V.