Involvement of histamine H4 and H1 receptors in scratching induced by histamine receptor agonists in Balb C mice

Br J Pharmacol. 2004 May;142(2):374-80. doi: 10.1038/sj.bjp.0705754. Epub 2004 Apr 5.


The role of histamine H(1), H(2), H(3) and H(4) receptors in acute itch induced by histamine was investigated in female BalbC mice. Scratching was induced by intradermal injections of pruritogen into the back of the neck and "itch" assessed by quantifying the scratching evoked. Histamine (0.03-80 micromol), histamine-trifluoromethyl-toluidine (HTMT, H(1) agonist, 0.002-2 micromol), clobenpropit (H(4) agonist, H(3) antagonist, 0.002-0.6 micromol) and to a lesser extent imetit (H(3)/H(4) agonist, 0.03-3 micromol) all induced dose-dependent scratching. Dimaprit (H(2) agonist, 0.04-40 micromol) did not cause scratching. Mepyramine (H(1) antagonist, 20 mg kg(-1), i.p.) reduced scratching evoked by histamine and HTMT, but not that caused by H(3) or H(4) agonists. Thioperamide (H(3)/H(4) antagonist, 20 mg kg(-1), i.p.) reduced scratching induced by histamine, H(3) and H(4) agonists, but not that caused by HTMT. The non-sedating H(1) antagonist, terfenadine, also significantly reduced the scratching induced by the H(1) agonist, HTMT. Cimetidine (H(2) antagonist, 20 mg kg(-1), i.p.) did not affect histamine-induced scratching. These results indicate that activation of histamine H(4) receptors causes itch in mice, in addition to the previously recognised role for H(1) receptors in evoking itch. Histamine H(4) receptor antagonists therefore merit investigation as antipruritic agents.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Female
  • Histamine / pharmacology
  • Histamine / toxicity
  • Histamine Agonists / pharmacology
  • Histamine Agonists / toxicity*
  • Mice
  • Mice, Inbred BALB C
  • Pruritus / chemically induced*
  • Pruritus / physiopathology
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / physiology*
  • Receptors, Histamine / physiology*
  • Receptors, Histamine H1 / physiology*
  • Receptors, Histamine H4


  • Histamine Agonists
  • Hrh4 protein, mouse
  • Receptors, G-Protein-Coupled
  • Receptors, Histamine
  • Receptors, Histamine H1
  • Receptors, Histamine H4
  • Histamine