title: Cloning and pharmacological characterization of the dog histamine H4 receptor.
abstract: The histamine H4 receptor has been shown to have a role in chemotaxis and mediator release in various types of immune cells and has been implicated in mediating inflammation in vivo. Previous work has shown that there were differences in the histamine H4 receptor sequence of different species and these translated into changes in the pharmacology of the receptors. To help further understand the nature of these differences, we have cloned and expressed the histamine H4 receptor of dog (Canis familiaris). The dog histamine H4 receptor has a 61-71% homology with the receptors from other species, with a 71% homology to the human receptor. The affinity for histamine at the dog histamine H4 receptor is 18 nM and is 3-fold lower than the human ortholog. A number of previously described histamine H4 receptor ligands were tested for affinity at the dog histamine H4 receptor and histamine showed the highest affinity of the ligands tested. In addition, the histamine H4 receptor selective antagonist, JNJ 7777120, had a Ki value of 50 nM and acts as an antagonist at the dog receptor. In general, agonists of the human histamine H4 receptor were also agonists of the dog receptor albeit with different efficacy levels. The cloning and in vitro pharmacological characterization of the dog histamine H4 receptor provide useful information for future studies using dog models as well as in understanding the ligand-receptor interactions of the receptor.
authors.affiliation: Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121, United States.
authors.forename: Wen
authors.initials: W
authors.lastname: Jiang
authors.forename: Herman D
authors.initials: HD
authors.lastname: Lim
authors.forename: Mai
authors.initials: M
authors.lastname: Zhang
authors.forename: Pragnya
authors.initials: P
authors.lastname: Desai
authors.forename: Heng
authors.initials: H
authors.lastname: Dai
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Colling
authors.forename: Rob
authors.initials: R
authors.lastname: Leurs
authors.forename: Robin L
authors.initials: RL
authors.lastname: Thurmond
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004285:Dogs; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D006168:Guinea Pigs; D000882:Haplorhini; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D007211:Indoles / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D010879:Piperazines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011869:Radioligand Assay; D051381:Rats; D011968:Receptors, Histamine / Q000187:drug effects* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine
chemical_list: D018076:DNA, Complementary; D017442:Histamine Agonists; D006633:Histamine Antagonists; D007202:Indicators and Reagents; D007211:Indoles; D008024:Ligands; D010879:Piperazines; D012333:RNA, Messenger; D011968:Receptors, Histamine; C484309:1-((5-chloro-1H-indol-2-yl)carbonyl)-4-methylpiperazine; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases