Histamine is a well known mediator of allergic
skin diseases and, with the discovery of the
histamine H(4) receptor, the role of
histamine is re-evaluated. There are only limited published data elucidating the role of the
histamine H(4) receptor in dogs. Twelve beagles intradermally injected with
histamine (0.25 micromol and 2.5 micromol/site) reacted with a classical wheal and flare reaction. None of the dogs showed signs of
pruritus. The dogs reacted with a wheal and flare reaction after
intradermal injection of
histamine H(4) receptor agonist/H(3) receptor antagonist
clobenpropit (0.1 micromol) and selective
histamine H(4) receptor agonist
VUF 8430 (1.5 micromol). Again, no scratching occurred in any of the dogs. The highly selective
histamine H(4) receptor antagonist
JNJ 7777120 reduced the
histamine-induced wheal reaction in nine out of 12 dogs. To determine whether canine mast cells are susceptible to
histamine H(4) receptor-mediated reactions, effects of
clobenpropit and
VUF 8430 were tested in canine
mastocytoma cells (C2). Incubation with
histamine H(4) receptor agonists (up to 10 micromol/L) induced a distinct
calcium(2+) influx. C2 cells also responded with enhanced chemotaxis when stimulated with
histamine,
VUF 8430 and
clobenpropit. Neither
VUF 8430, nor
clobenpropit (up to 10 micromol/L) led to a modulation of
histamine concentration in supernatants of canine
mastocytoma cells, whereas
mastoparan, used as a positive control, enhanced
histamine concentration in supernatants. For treatment of allergic
skin diseases in dogs, a combination of H(1)R and H(4)R antagonists might be advantageous.