Modulation of hematopoiesis through histamine receptor signaling

Front Biosci (Schol Ed). 2011 Jan 1;3:467-73. doi: 10.2741/s165.


Histamine is one of the most versatile biogenic amines targeting a variety of cells through extra- and intracellular binding sites and specific receptors, which trigger different signal transduction pathways. It has been associated with cell growth ever since G. Kahlson demonstrated that its synthesis was increased in rapidly growing tissues of plants and animals. He proposed that the newly formed amine, as opposed to its stored counterpart, might play a major role in growth processes. Later on, a number of investigators provided evidence for the contribution of histamine to the expansion of normal and malignant cells, whether of hematopoietic origin or not. These studies have generated conflicting results, revealing growth-promoting as well as inhibitory effects, most likely because the final outcome of exposure to histamine depends on the signaling pathways triggered by distinct receptors and their differential distribution among the target population. The purpose of the present review is to outline our current understanding of the regulatory functions of histamine during growth and differentiation of hematopoietic progenitors, focusing on those mediated through its H4 receptor.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Cycle / drug effects
  • Cell Cycle / physiology
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Hematopoiesis / physiology*
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / physiology
  • Histamine / metabolism*
  • Humans
  • Imidazoles / pharmacology
  • Mice
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Histamine / metabolism*
  • Receptors, Histamine H4
  • Signal Transduction / physiology*
  • Thiourea / analogs & derivatives
  • Thiourea / pharmacology


  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • HRH4 protein, human
  • Imidazoles
  • Receptors, G-Protein-Coupled
  • Receptors, Histamine
  • Receptors, Histamine H4
  • Histamine
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Thiourea
  • clobenpropit