Site-directed mutagenesis of the histamine H1-receptor reveals a selective interaction of asparagine207 with subclasses of H1-receptor agonists

Biochem Biophys Res Commun. 1994 May 30;201(1):295-301. doi: 10.1006/bbrc.1994.1701.

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 N tau-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 N pi-nitrogen atom is essential for H1-receptor activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asparagine / chemistry
  • Base Sequence
  • Chlorpheniramine / chemistry
  • DNA Primers / chemistry
  • Guinea Pigs
  • Histamine / chemistry
  • Histamine Agonists / chemistry*
  • Inositol Phosphates / metabolism
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Pyrilamine / chemistry
  • Receptors, Histamine H1 / chemistry*
  • Structure-Activity Relationship

Substances

  • DNA Primers
  • Histamine Agonists
  • Inositol Phosphates
  • Receptors, Histamine H1
  • Chlorpheniramine
  • Asparagine
  • Histamine
  • Pyrilamine