Yao Betty Bei, Sharma Rahul, Cassar Steven, Esbenshade Timothy A, Hancock Arthur A
Neuroscience Research, Global Pharmaceutical Research & Development, Abbott Laboratories, R4MN, AP9A, 100 Abbott Park Road, Abbott Park, IL 60064, USA.
Eur J Pharmacol. 2003 Dec 15;482(1-3):49-60. doi: 10.1016/j.ejphar.2003.09.072.
Species differences have been described previously for histamine H(3) receptor pharmacology. Rat selective histamine H(3) receptor ligands such as ciproxifan and A-304121 (2-amino-1-[4-[3-(4-cyclopropanecarbonyl-phenoxy)-propyl]-piperazin-1-yl]-propan-1-one) show over 100-fold selectivity for the rat receptor compared to the human receptor. To date, however, the pharmacology of the cloned monkey histamine H(3) receptor has not been examined. In this study, we cloned the monkey histamine H(3) receptor gene (H(3)R) and evaluated the receptor pharmacology in binding and functional assays. The monkey histamine H(3) receptor is highly homologous to the human receptor with 438 identities in their 445 amino acid sequences, but less homologous to the rat receptor. However, unlike the human or rat, we found no evidence for additional splicing for the monkey H(3)R. Pharmacological analysis indicated that the monkey receptor exhibited similar pharmacological profiles to those of the human receptor, providing critical information for characterizing histamine H(3) receptor ligands in monkey behavioral models.
组胺H(3)受体药理学的种属差异此前已有描述。大鼠选择性组胺H(3)受体配体，如西普司特和A-304121（2-氨基-1-[4-[3-(4-环丙烷羰基-苯氧基)-丙基]-哌嗪-1-基]-丙烷-1-酮），与人类受体相比，对大鼠受体表现出超过100倍的选择性。然而，迄今为止，克隆的猴组胺H(3)受体的药理学尚未得到研究。在本研究中，我们克隆了猴组胺H(3)受体基因（H(3)R），并在结合和功能试验中评估了该受体的药理学特性。猴组胺H(3)受体与人类受体高度同源，在其445个氨基酸序列中有438个相同，但与大鼠受体的同源性较低。然而，与人类或大鼠不同的是，我们没有发现猴H(3)R存在额外剪接的证据。药理学分析表明，猴受体表现出与人类受体相似的药理学特征，为在猴行为模型中表征组胺H(3)受体配体提供了关键信息。
