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Site-Directed Mutagenesis of the Histamine H1-Receptor Reveals a Selective Interaction of Asparagine207 with Subclasses of H1-Receptor Agonists

https://doi.org/10.1006/bbrc.1994.1701Get rights and content

Abstract

In this study we investigated the role of the threonine203 and the asparagine207 residues in the fifth transmembrane domain of the guinea-pig histamine H1-receptor by site-directed mutagenesis to non-functional alanines. Whereas the threonine203 residue is not important for the action of histamine, the asparagine207 residue appears to be involved in the binding of the Nτ-nitrogen atom of histamine and its 2-methyl-analogue, For the 2-phenyl-analogue and non-imidazole H1-receptor agonists, this residue is, however, not essential for binding. On the basis of this study we conclude that different histamine H1-receptor agonists interact in different ways with the H1-receptor protein. Moreover, we speculate that the interaction with the Nπ-nitrogen atom is essential for H1-receptor activation.

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