Comparison of Human, Mouse, Rat, and Guinea Pig Histamine H4 Receptors Reveals Substantial Pharmacological Species Variation

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 299; no. 1; pp. 121 - 130
• Main Authors: Liu, C, Wilson, S J, Kuei, C, Lovenberg, T W
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01.10.2001
• Subjects: Amino Acid Sequence; Animals; Calcium - metabolism; Cell Line; Cloning, Molecular; COS Cells; Cyclic AMP - metabolism; DNA Fragmentation; Guinea Pigs; Humans; Mice; Molecular Sequence Data; Radioligand Assay; Rats; Receptors, G-Protein-Coupled; Receptors, Histamine - drug effects; Receptors, Histamine - genetics; Receptors, Histamine H4; Reverse Transcriptase Polymerase Chain Reaction; Species Specificity; Transfection
• ISSN: 0022-3565; 1521-0103

The recently identified histamine H 4 receptor has revealed a potential new complexity for the role of histamine in the immune system. To begin to understand the role of this receptor in humans, one must first determine whether homologs exist and can be studied in lower species. To address this, we cloned the rat, mouse, and guinea pig cDNAs corresponding to the recently identified human histamine H 4 receptor. The rat, mouse, and guinea pig H 4 sequences are significantly different from the human H 4 sequence at 69, 68, and 65% homology, respectively. The tissue distribution of the rat, mouse, and guinea pig H 4 receptors is similar to human in that bone marrow and spleen are the most abundant sources of expression. The human and guinea pig H 4 receptors display the highest binding affinity for [ 3 H]histamine ( K D = 5 nM each), whereas the affinities for rat and mouse receptors are substantially lower at 136 and 42 nM, respectively. With respect to the pharmacological profile of known H 3 /H 4 ligands, even greater differences in binding affinities exist among the species homologs. There are also substantial differences in the signal transduction response to each of the four species of H 4 receptor. This work demonstrates the existence of histamine H 4 receptors in lower species and demonstrates that a clear knowledge of each species pharmacological profile will be essential to elucidate the role of this receptor subtype in vivo.