Cloning and Pharmacological Characterization of a Fourth Histamine Receptor (H4) Expressed in Bone Marrow

• DOI: 10.1124/mol.59.3.420
• Publication Date: 2018-01-08T20:41:59Z
• Authors: Changlu Liu; Xiao-Jun Ma; Xiaoxia Jiang; Sandy J. Wilson; Claudia L. Hofstra; Jonathan Blevitt; Jayashree Pyati; Xiaobing Li; Wenying Chai; Nicholas Carruthers; Timothy W. Lovenberg
• Keywords: Loratadine; Histamine H4 receptor; Dimaprit

Histamine is a multifunctional hormone that regulates smooth muscle contraction in the airways, acid secretion gut, and neurotransmitter release central nervous system through three well characterized receptor subtypes, H(1), H(2), H(3), respectively. As part of directed effort to discover novel G-protein-coupled receptors homology searching genomic databases, we identified partial clone (GPCR105) had significant recently histamine H(3) cDNA. Expression full-length human GPCR105 cells confers ability bind [(3)H]histamine with high affinity (K(D) = 5 nM). pharmacologically similar it binds many known agonists antagonists, albeit different rank order affinity/potency. does not (i.e., K(D) > 10 microM) all tested H(1) H(2) antagonists such as diphenhydramine, loratadine, ranitidine, cimetidine, but has modest for agonist, dimaprit (377 Whereas expressed almost exclusively tissues, GPRC105 primarily bone marrow eosinophils. Together, these data demonstrate structurally related receptor. However, its unique expression profile physiological role suggest fourth subtype (H(4)) may be therapeutic target regulation immune function, particularly respect allergy asthma.