Involvement of histamine H 4 and H 1 receptors in scratching induced by histamine receptor agonists in BalbC mice

Abstract

1. 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. 2. Histamine (0.03-80 μmol), histamine-trifluoromethyl- toluidine (HTMT, H 1 agonist, 0.002-2μmol), clobenpropit (H 4 agonist, H 3 antagonist, 0.002-0.6 μmol) and to a lesser extent imetit (H 3/ H 4 agonist, 0.03-3 μmol) all induced dose-dependent scratching. Dimaprit (H 2 agonist, 0.04-40 μmol) did not cause scratching. 3. 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. 4. 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.