Lysine200 located in the fifth transmembrane domain of the histamine H1 receptor interacts with histamine but not with all H1 agonists

Biochem Biophys Res Commun. 1995 Sep 5;214(1):110-7. doi: 10.1006/bbrc.1995.2263.


Previously, we have shown that asparagine207 in the fifth transmembrane domain of the histamine H1 receptor is crucial for the binding of the N tau-nitrogen of the imidazole ring of histamine (Leurs et al., Biochem. Biophys. Res. Commun., 201, 295, 1994). In view of the potential interaction of the imidazole ring of histamine with a binding site, formed by asparagine207 and lysine200, we mutated lysine200 in the fifth transmembrane domain of the histamine H1 receptor to a non-functional alanine residue. This mutation did not affect the binding of the tested H1 receptor antagonists but resulted in a 5-fold lower affinity for histamine. The binding of other H1 receptor agonists was not affected. In stably transfected CHO cells histamine was 55-fold less effective in activating the H1Lys200Ala receptor (EC50 = 66 microM) compared to the wild type H1 receptor (EC50 = 1.2 microM). Receptor activation by the 2-methyl and the 2-(3-bromophenyl)-analogues however was hardly affected by the mutation, indicating that the 2-substituent probably prevents the interaction with the lysine200 residue. Finally, the Lys200Ala mutation reduced the production of [3H]inositol phosphates, stimulated by the non-imidazole H1 receptor agonist 2-pyridylethylamine. These data indicate that lysine200 interacts with the N pi-nitrogen of histamine and is important for the activation of the H1 receptor by histamine and the non-imidazole agonist 2-pyridylethylamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • Cell Membrane / chemistry
  • DNA Primers
  • Guinea Pigs
  • Histamine / chemistry*
  • Histamine Agonists / chemistry*
  • Humans
  • Lysine / chemistry*
  • Molecular Sequence Data
  • Receptors, Histamine H1 / chemistry*
  • Sequence Homology, Amino Acid


  • DNA Primers
  • Histamine Agonists
  • Receptors, Histamine H1
  • Histamine
  • Lysine