Comparison of Human, Mouse, Rat, and Guinea Pig Histamine H4 Receptors Reveals Substantial Pharmacological Species Variation
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...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 299; no. 1; pp. 121 - 130 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Pharmacology and Experimental Therapeutics
01.10.2001
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-3565 1521-0103 |