Molecular and cellular analysis of human histamine receptor subtypes

Trends Pharmacol Sci. 2013 Jan;34(1):33-58. doi: 10.1016/ Epub 2012 Dec 17.


The human histamine receptors hH(1)R and hH(2)R constitute important drug targets, and hH(3)R and hH(4)R have substantial potential in this area. Considering the species-specificity of pharmacology of H(x)R orthologs, it is important to analyze hH(x)Rs. Here, we summarize current knowledge of hH(x)Rs endogenously expressed in human cells and hH(x)Rs recombinantly expressed in mammalian and insect cells. We present the advantages and disadvantages of the various systems. We also discuss problems associated with the use of hH(x)R antibodies, an issue of general relevance for G-protein-coupled receptors (GPCRs). There is much greater overlap in activity of 'selective' ligands for other hH(x)Rs than the cognate receptor subtype than generally appreciated. Studies with native and recombinant systems support the concept of ligand-specific receptor conformations, encompassing agonists and antagonists. It is emerging that for characterization of hH(x)R ligands, one cannot rely on a single test system and a single parameter. Rather, multiple systems and parameters have to be studied. Although such studies are time-consuming and expensive, ultimately, they will increase drug safety and efficacy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Histamine Agonists / chemistry
  • Histamine Agonists / pharmacology
  • Histamine Antagonists / chemistry
  • Histamine Antagonists / pharmacology
  • Humans
  • Molecular Targeted Therapy
  • Receptors, Histamine / chemistry*
  • Receptors, Histamine / classification*
  • Receptors, Histamine / genetics
  • Receptors, Histamine / metabolism


  • Histamine Agonists
  • Histamine Antagonists
  • Receptors, Histamine