Cloning and pharmacological characterization of the dog histamine H 4 receptor

Abstract

The histamine H 4 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 H 4 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 H 4 receptor of dog ( Canis familiaris). The dog histamine H 4 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 H 4 receptor is 18 nM and is 3-fold lower than the human ortholog. A number of previously described histamine H 4 receptor ligands were tested for affinity at the dog histamine H 4 receptor and histamine showed the highest affinity of the ligands tested. In addition, the histamine H 4 receptor selective antagonist, JNJ 7777120, had a K i value of 50 nM and acts as an antagonist at the dog receptor. In general, agonists of the human histamine H 4 receptor were also agonists of the dog receptor albeit with different efficacy levels. The cloning and in vitro pharmacological characterization of the dog histamine H 4 receptor provide useful information for future studies using dog models as well as in understanding the ligand–receptor interactions of the receptor.