Rossbach Kristine, Stark Holger, Sander Kerstin, Leurs Rob, Kietzmann Manfred, Bäumer Wolfgang
Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, 30559 Hannover, Germany.
Vet Dermatol. 2009 Oct;20(5-6):555-61. doi: 10.1111/j.1365-3164.2009.00854.x.
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.
组胺是过敏性皮肤病中一种广为人知的介质，随着组胺H(4)受体的发现，组胺的作用被重新评估。目前仅有有限的已发表数据阐明组胺H(4)受体在犬类中的作用。12只比格犬皮内注射组胺（0.25微摩尔和2.5微摩尔/部位）后出现典型的风团和潮红反应。没有一只犬表现出瘙痒迹象。犬皮内注射组胺H(4)受体激动剂/ H(3)受体拮抗剂氯苯丙哌嗪（0.1微摩尔）和选择性组胺H(4)受体激动剂VUF 8430（1.5微摩尔）后出现风团和潮红反应。同样，没有一只犬出现抓挠行为。高选择性组胺H(4)受体拮抗剂JNJ 7777120使12只犬中的9只组胺诱导的风团反应减弱。为了确定犬肥大细胞是否对组胺H(4)受体介导的反应敏感，在犬肥大细胞瘤细胞（C2）中测试了氯苯丙哌嗪和VUF 8430的作用。用组胺H(4)受体激动剂（高达10微摩尔/升）孵育诱导了明显的钙(2+)内流。当用组胺、VUF 8430和氯苯丙哌嗪刺激时，C2细胞也表现出趋化性增强。VUF 8430和氯苯丙哌嗪（高达10微摩尔/升）均未导致犬肥大细胞瘤细胞上清液中组胺浓度的调节，而用作阳性对照的蜂毒肽则增加了上清液中的组胺浓度。对于犬过敏性皮肤病的治疗，H(1)R和H(4)R拮抗剂联合使用可能具有优势。
