Discovery of a novel member of the histamine receptor family.
Article Details
- CitationCopy to clipboard
Nguyen T, Shapiro DA, George SR, Setola V, Lee DK, Cheng R, Rauser L, Lee SP, Lynch KR, Roth BL, O'Dowd BF
Discovery of a novel member of the histamine receptor family.
Mol Pharmacol. 2001 Mar;59(3):427-33.
- PubMed ID
- 11179435 [ View in PubMed]
- Abstract
We report the discovery, tissue distribution and pharmacological characterization of a novel receptor, which we have named H4. Like the three histamine receptors reported previously (H1, H2, and H3), the H4 receptor is a G protein-coupled receptor and is most closely related to the H3 receptor, sharing 58% identity in the transmembrane regions. The gene encoding the H4 receptor was discovered initially in a search of the GenBank databases as sequence fragments retrieved in a partially sequenced human genomic contig mapped to chromosome 18. These sequences were used to retrieve a partial cDNA clone and, in combination with genomic fragments, were used to determine the full-length open reading frame of 390 amino acids. Northern analysis revealed a 3.0-kb transcript in rat testis and intestine. Radioligand binding studies indicated that the H4 receptor has a unique pharmacology and binds [(3)H]histamine (K(d) = 44 nM) and [(3)H]pyrilamine (K(d) = 32 nM) and several psychoactive compounds (amitriptyline, chlorpromazine, cyproheptadine, mianserin) with moderate affinity (K(i) range of 33-750 nM). Additionally, histamine induced a rapid internalization of HA-tagged H4 receptors in transfected human embryonic kidney 293 cells.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Amitriptyline Histamine H4 receptor Protein Humans UnknownBinderDetails Chlorpromazine Histamine H4 receptor Protein Humans UnknownBinderDetails - Binding Properties
Drug Target Property Measurement pH Temperature (°C) Amitriptyline Histamine H4 receptor Ki (nM) 33.6 N/A N/A Details Chlorpromazine Histamine H4 receptor Ki (nM) 50.2 N/A N/A Details Clozapine Histamine H4 receptor Ki (nM) 849.6 N/A N/A Details Doxepin Histamine H4 receptor Ki (nM) 105.9 N/A N/A Details Mianserin Histamine H4 receptor Ki (nM) 750 N/A N/A Details