H<sub>4</sub> receptor | Histamine receptors | IUPHAR/BPS Guide to PHARMACOLOGY

H4 receptor

Target id: 265

Nomenclature: H4 receptor

Family: Histamine receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     H4 receptor has curated GtoImmuPdb data

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 390 18q11.2 HRH4 histamine receptor H4 2,25-26,28
Mouse 7 391 18 A1 Hrh4 histamine receptor H4 23
Rat 7 391 18p13 Hrh4 histamine receptor H4 23
Previous and Unofficial Names
GPCR105 [22] | HH4R [26] | H4R
Database Links
Specialist databases
GPCRDB hrh4_human (Hs), hrh4_mouse (Mm), hrh4_rat (Rn)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
histamine

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]histamine Hs Full agonist 7.4 – 8.4 pKd 10,22-23,25,28,30
pKd 7.4 – 8.4 [10,22-23,25,28,30]
N-[3H]methylhistamine Hs Full agonist 7.8 pKd 22
pKd 7.8 [22]
[125I]CCL16 (human) Hs Full agonist 7.8 pKd 27
pKd 7.8 [27]
[3H]histamine Mm Full agonist 7.4 pKd 23
pKd 7.4 [23]
[3H](R)-α-methylhistamine Hs Full agonist 7.2 pKd 22
pKd 7.2 [22]
[3H]histamine Rn Full agonist 6.9 pKd 23
pKd 6.9 [23]
imetit Hs Full agonist 8.2 – 8.9 pKi 22-23,25,42
pKi 8.2 – 8.9 [22-23,25,42]
imetit Mm Full agonist 8.2 pKi 23
pKi 8.2 [23]
imetit Rn Full agonist 8.2 pKi 23
pKi 8.2 [23]
histamine Hs Full agonist 7.8 – 8.3 pKi 10,19,22-23,25,38,42
pKi 7.8 – 8.3 [10,19,22-23,25,38,42]
ST-1006 Hs Agonist 7.9 pKi 31
pKi 7.9 [31]
clobenpropit Hs Partial agonist 7.4 – 8.3 pKi 7,19,22-23,25
pKi 7.4 – 8.3 (Ki 3.98x10-8 – 5.01x10-9 M) [7,19,22-23,25]
clobenpropit Mm Partial agonist 7.8 pKi 23
pKi 7.8 [23]
immepip Hs Full agonist 7.6 – 8.0 pKi 16,22,42
pKi 7.6 – 8.0 [16,22,42]
impromidine Hs Partial agonist 7.6 – 7.9 pKi 19,22
pKi 7.6 – 7.9 [19,22]
4-methylhistamine Hs Full agonist 7.3 – 8.2 pKi 10,19
pKi 7.3 – 8.2 (Ki 5.01x10-8 – 6.31x10-9 M) [10,19]
VUF 8430 Hs Full agonist 7.5 pKi 18
pKi 7.5 (Ki 3.16x10-8 M) [18]
N-methylhistamine Hs Full agonist 7.3 – 7.6 pKi 10,22-23
pKi 7.3 – 7.6 [10,22-23]
histamine Mm Full agonist 7.4 pKi 23
pKi 7.4 [23]
histamine Rn Full agonist 7.2 pKi 23
pKi 7.2 [23]
clobenpropit Rn Partial agonist 7.2 pKi 23
pKi 7.2 [23]
N-α-methylhistamine Hs Full agonist 6.8 – 7.2 pKi 25,42
pKi 6.8 – 7.2 [25,42]
(R)-α-methylhistamine Hs Full agonist 6.5 – 6.9 pKi 22-23,25,42
pKi 6.5 – 6.9 [22-23,25,42]
N-ethylhistamine Hs Full agonist 6.7 pKi 10
pKi 6.7 [10]
N-methylhistamine Mm Full agonist 6.5 pKi 23
pKi 6.5 [23]
(R)-α-methylhistamine Mm Full agonist 6.4 pKi 23
pKi 6.4 [23]
2-methylhistamine Hs Full agonist 6.1 – 6.6 pKi 10,19
pKi 6.1 – 6.6 [10,19]
N-methylhistamine Rn Full agonist 6.3 pKi 23
pKi 6.3 [23]
(R)-α-methylhistamine Rn Full agonist 6.2 pKi 23
pKi 6.2 [23]
2-(3-bromophenyl)histamine Hs Full agonist 6.0 pKi 19
pKi 6.0 [19]
N,N-dimethylhistamine Hs Full agonist 5.9 pKi 10
pKi 5.9 [10]
HTMT Hs Full agonist 5.9 pKi 42
pKi 5.9 [42]
dimaprit Hs Full agonist 4.9 – 6.5 pKi 19,22,25,42
pKi 4.9 – 6.5 [19,22,25,42]
methimepip Hs Full agonist 5.7 pKi 15
pKi 5.7 [15]
(S)-α-methylhistamine Hs Full agonist 5.5 pKi 25
pKi 5.5 [25]
improgan Hs Full agonist 5.2 pKi 42
pKi 5.2 [42]
CCL16 {Sp: Human} Hs Full agonist 8.1 pIC50 27
pIC50 8.1 [27]
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]JNJ 7777120 Hs Antagonist 8.4 pKd 40
pKd 8.4 (Kd 3.6x10-9 M) [40]
[3H]pyrilamine Hs Antagonist 7.5 pKd 28
pKd 7.5 [28]
ZPL-3893787 Hs Antagonist 8.3 pKi 31
pKi 8.3 [31]
INCB-38579 Hs Antagonist 8.3 pKi 31
pKi 8.3 [31]
JNJ 7777120 Hs Antagonist 7.8 – 8.3 pKi 19,36,40
pKi 7.8 – 8.3 (Ki 1.58x10-8 – 5.01x10-9 M) [19,36,40]
JNJ-39758979 Hs Antagonist 7.9 pKi 31,34
pKi 7.9 (Ki 1.25x10-8 M) [31,34]
iodophenpropit Hs Antagonist 7.7 pKi 42
pKi 7.7 [42]
JNJ-10191584 Hs Antagonist 7.7 pKi 38
pKi 7.7 [38]
thioperamide Mm Antagonist 7.6 pKi 23
pKi 7.6 [23]
thioperamide Rn Antagonist 7.6 pKi 23
pKi 7.6 [23]
toreforant Hs Antagonist 7.1 pKi 5
pKi 7.1 (Ki 8.3x10-8 M) [5]
Description: Displacament of histamine from human H4 recepotor expressed in mammalian cells.
burimamide Hs Antagonist 6.7 – 7.4 pKi 19,22-23,25,42
pKi 6.7 – 7.4 [19,22-23,25,42]
thioperamide Hs Antagonist 6.3 – 7.6 pKi 6-7,22-23,25,42
pKi 6.3 – 7.6 Selective for H3/H4 compared to H1 and H3. [6-7,22-23,25,42]
clozapine Hs Antagonist 6.2 – 6.7 pKi 19,22-23,42
pKi 6.2 – 6.7 [19,22-23,42]
burimamide Mm Antagonist 6.1 pKi 23
pKi 6.1 [23]
burimamide Rn Antagonist 6.0 pKi 23
pKi 6.0 [23]
ciproxifan Hs Antagonist 5.7 pKi 6-7,31
pKi 5.7 [6-7,31]
clozapine Rn Antagonist 5.7 pKi 23
pKi 5.7 [23]
clozapine Mm Antagonist 5.5 pKi 23
pKi 5.5 [23]
MK-0249 Hs Antagonist <5.0 pKi 31
pKi <5.0 (Ki >1x10-5 M) [31]
conessine Hs Antagonist <5.0 pKi 31
pKi <5.0 (Ki >1x10-5 M) [31]
pitolisant Hs Antagonist <4.0 pKi 31
pKi <4.0 (Ki >1x10-4 M) [31]
H4 antagonist 48 Hs Antagonist 7.6 pIC50 17
pIC50 7.6 (IC50 2.7x10-8 M) [17]
Description: Radioligand competitive binding assay using [3H]Histamine as tracer, and membrane preparations from CHO-K1 cells expressing human H4 receptor.
H4 antagonist 48 Mm Antagonist 6.5 pIC50 17
pIC50 6.5 (IC50 2.9x10-7 M) [17]
Description: Radioligand competitive binding assay using [3H]Histamine as tracer, and membrane preparations from CHO-K1 cells expressing mouse H4 receptor.
View species-specific antagonist tables
Antagonist Comments
H4 antagonist 48 exhibits no appreciable binding to the H1, H2 or H3 receptors (IC50s >10 μM) [17].
Immunopharmacology Comments
H4 receptor is primarily expressed in mast cells and eosinophils, but is also found on human neutrophils and basophils, and plays an important role in modulating eosinophil chemotaxis [29,41]. H4 receptor acts in concert with H2 receptor to enhance IL-16 production in lymphocytes [32]. In mast cells, selective H4 receptor activation increases calcium influx, degranulation, cytokine release and leukotriene production (cysteinyl and LTB4) [14]. In comparison to the H1 receptor, the H4 receptor is a relatively new therapeutic target for inflammation [3,8,39]. Selective H4 receptor antagonists are in development for potential clinical use, in particular for the treatment of Th2-dependent dermal inflammation such as atopic dermatitis (see for example H4 antagonist 48), and asthma [12].
Cell Type Associations
Immuno Cell Type:  Granulocytes
Cell Ontology Term:   eosinophil (CL:0000771)
Comment:  Eosinophils express all four histamine receptor subtypes.
References:  11,24
Immuno Cell Type:  Mast cells
Cell Ontology Term:   mast cell (CL:0000097)
Comment:  In humans, mast cells express H1R, H2R and H4R.
References:  9
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0006954 inflammatory response IBA
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Phospholipase C stimulation
References:  13
Tissue Distribution
Bone marrow and spleen.
Species:  Human
Technique:  RNase protection assay.
References:  22
Gastrointestinal tract.
Species:  Human
Technique:  qRT-PCR and immunohistochemistry.
References:  33
Eosinophils.
Species:  Human
Technique:  Northern blotting.
References:  22
Monocytes.
Species:  Human
Technique:  Flow cytometry.
References:  4
Peripheral blood leukocytes, thymus, small intestine, spleen, and colon.
Species:  Human
Technique:  RT-PCR.
References:  30
Leukocyte, spleen, lung, liver > heart, skeletal muscle.
Brain: cerebellum, hippocampus.
Species:  Human
Technique:  RT-PCR.
References:  2
Eosinophils.
Species:  Human
Technique:  RT-PCR.
References:  27
Mast cells.
Species:  Human
Technique:  RT-PCR.
References:  21
Eosinophils and dendritic cells.
Species:  Human
Technique:  RT-PCR.
References:  20
Mast cells and eosinophils.
Species:  Mouse
Technique:  RT-PCR and Northern Blotting.
References:  13
Eosinophils.
Species:  Mouse
Technique:  RT-PCR.
References:  27
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Measurement of cAMP levels in SK-N-MC cells transfected with the human H4 receptor using a cAMP-sensitive reporter gene.
Species:  Human
Tissue:  SK-N-MC cells.
Response measured:  Inhibition of cAMP accumulation.
References:  19,22-23
Measurement of Ca2+ levels in mouse mast cells endogenously expressing the H4 receptor.
Species:  Mouse
Tissue:  Mast cells.
Response measured:  Ca2+ mobilisation from intracellular stores.
References:  13
Measurement of cAMP levels in HEK 293 cells transfected with the human H4 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  10,26
Measurement of Ca2+ levels in HEK 293 cells transfected with the human H4 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Ca2+ mobilisation.
References:  25,35
Measurement of MAPK activity in HEK 293 cells transfected with the human H4 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Stimulation of MAPK activity.
References:  25
Measurement of Ca2+ levels in human monocytes endogenously expressing the H4 receptor.
Species:  Human
Tissue:  Monocytes.
Response measured:  Stimulation of Ca2+ mobilisation.
References:  4
Physiological Functions
Eosinophil shape change.
Species:  Human
Tissue:  Eosinophils.
References:  1,20
Upregulation of cell surface adhesion molecules.
Species:  Human
Tissue:  Eosinophils.
References:  20
Chemotaxis.
Species:  Human
Tissue:  Eosinophils.
References:  20
Chemotaxis.
Species:  Mouse
Tissue:  Mast cells.
References:  13
Eosinophil trafficking.
Species:  Mouse
Tissue:  In vivo.
References:  27
Zymosan-induced neutrophil release from bone marrow.
Species:  Mouse
Tissue:  In vivo.
References:  37
Inhibition of CCL2 production.
Species:  Human
Tissue:  Monocytes.
References:  4
Physiological Consequences of Altering Gene Expression
Chemotaxis is not seen in mast cells from H4 receptor knockout mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  13
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Hrh4tm1Lex Hrh4tm1Lex/Hrh4tm1Lex
involves: 129S/SvEv * BALB/c
MGI:2429635  MP:0008721 abnormal chemokine level PMID: 16709868 
Hrh4tm1Lex Hrh4tm1Lex/Hrh4tm1Lex
involves: 129S/SvEv * BALB/c
MGI:2429635  MP:0002376 abnormal dendritic cell physiology PMID: 16709868 
Hrh4tm1Lex Hrh4tm1Lex/Hrh4tm1Lex
involves: 129S/SvEv * BALB/c
MGI:2429635  MP:0008751 abnormal interleukin level PMID: 16709868 
Hrh4tm1Lex Hrh4tm1Lex/Hrh4tm1Lex
involves: 129S/SvEv * C57BL/6
MGI:2429635  MP:0002423 abnormal mast cell physiology PMID: 16709868 
Hrh4+|Hrh4tm1Lex Hrh4tm1Lex/Hrh4+
involves: 129S/SvEv * C57BL/6
MGI:2429635  MP:0002423 abnormal mast cell physiology PMID: 12626656 
Hrh4tm1Lex Hrh4tm1Lex/Hrh4tm1Lex
involves: 129S/SvEv * BALB/c
MGI:2429635  MP:0002492 decreased IgE level PMID: 16709868 
Hrh4tm1Lex Hrh4tm1Lex/Hrh4tm1Lex
involves: 129S/SvEv * BALB/c
MGI:2429635  MP:0008495 decreased IgG1 level PMID: 16709868 
Hrh4tm1Lex Hrh4tm1Lex/Hrh4tm1Lex
involves: 129S/SvEv * BALB/c
MGI:2429635  MP:0001876 decreased inflammatory response PMID: 16709868 

References

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1. Buckland KF, Williams TJ, Conroy DM. (2003) Histamine induces cytoskeletal changes in human eosinophils via the H(4) receptor. Br J Pharmacol, 140: 1117-1127. [PMID:14530216]

2. Cogé F, Guénin SP, Rique H, Boutin JA, Galizzi JP. (2001) Structure and expression of the human histamine H4-receptor gene. Biochem Biophys Res Commun, 284: 301-309. [PMID:11394877]

3. de Esch IJ, Thurmond RL, Jongejan A, Leurs R. (2005) The histamine H4 receptor as a new therapeutic target for inflammation. Trends Pharmacol. Sci., 26 (9): 462-9. [PMID:16054239]

4. Dijkstra D, Leurs R, Chazot P, Shenton FC, Stark H, Werfel T, Gutzmer R. (2007) Histamine downregulates monocyte CCL2 production through the histamine H(4) receptor. J Allergy Clin Immunol,: -. [PMID:17507084]

5. Edwards JP, Kindrachuk DE, Venable JD, Mapes CM, Pippel DJ,. (2007) Benzoimidazol-2-yl pyrimidines and pyrazines as modulators of the histamine H4 receptor. Patent number: WO2007117399. Assignee: Janssen Pharmaceutica Nv. Priority date: 31/03/2006. Publication date: 18/10/2007.

6. Esbenshade TA, Fox GB, Krueger KM, Baranowski JL, Miller TR, Kang CH, Denny LI, Witte DG, Yao BB, Pan JB, Faghih R, Bennani YL, Williams M, Hancock AA. (2004) Pharmacological and behavioral properties of A-349821, a selective and potent human histamine H3 receptor antagonist. Biochem Pharmacol, 68: 933-945. [PMID:15294456]

7. Esbenshade TA, Krueger KM, Miller TR, Kang CH, Denny LI, Witte DG, Yao BB, Fox GB, Faghih R, Bennani YL, Williams M, Hancock AA. (2003) Two novel and selective nonimidazole histamine H3 receptor antagonists A-304121 and A-317920: I. In vitro pharmacological effects. J Pharmacol Exp Ther, 305: 887-896. [PMID:12606603]

8. Fung-Leung WP, Thurmond RL, Ling P, Karlsson L. (2004) Histamine H4 receptor antagonists: the new antihistamines?. Curr Opin Investig Drugs, 5 (11): 1174-83. [PMID:15573868]

9. Gangwar RS, Landolina N, Arpinati L, Levi-Schaffer F. (2017) Mast cell and eosinophil surface receptors as targets for anti-allergic therapy. Pharmacol. Ther., 170: 37-63. [PMID:27773785]

10. Gbahou F, Vincent L, Humbert-Claude M, Tardivel-Lacombe J, Chabret C, Arrang JM. (2006) Compared pharmacology of human histamine H3 and H4 receptors: structure-activity relationships of histamine derivatives. Br J Pharmacol, 147: 744-754. [PMID:16432504]

11. Gibbs BF, Levi-Schaffer F. (2012) H₄ receptors in mast cells and basophils: a new therapeutic target for allergy?. Front Biosci (Landmark Ed), 17: 430-7. [PMID:22201753]

12. Hartwig C, Munder A, Glage S, Wedekind D, Schenk H, Seifert R, Neumann D. (2015) The histamine H4 -receptor (H4 R) regulates eosinophilic inflammation in ovalbumin-induced experimental allergic asthma in mice. Eur. J. Immunol., 45 (4): 1129-40. [PMID:25501767]

13. Hofstra CL, Desai PJ, Thurmond RL, Fung-Leung WP. (2003) Histamine H4 receptor mediates chemotaxis and calcium mobilization of mast cells. J Pharmacol Exp Ther, 305: 1212-1221. [PMID:12626656]

14. Jemima EA, Prema A, Thangam EB. (2014) Functional characterization of histamine H4 receptor on human mast cells. Mol. Immunol., 62 (1): 19-28. [PMID:24934979]

15. Kitbunnadaj R, Hashimoto T, Poli E, Zuiderveld OP, Menozzi A, Hidaka R, de Esch IJ, Bakker RA, Menge WM, Yamatodani A, Coruzzi G, Timmerman H, Leurs R. (2005) N-substituted piperidinyl alkyl imidazoles: discovery of methimepip as a potent and selective histamine H3 receptor agonist. J Med Chem, 48: 2100-2107. [PMID:15771452]

16. Kitbunnadaj R, Zuiderveld OP, de Esch IJ, Vollinga RC, Bakker R, Lutz M, Spek AL, Cavoy E, Deltent MF, Menge WM, Timmerman H, Leurs R. (2003) Synthesis and structure-activity relationships of conformationally constrained histamine H(3) receptor agonists. J Med Chem, 46: 5445-5457. [PMID:14640553]

17. Ko K, Kim HJ, Ho PS, Lee SO, Lee JE, Min CR, Kim YC, Yoon JH, Park EJ, Kwon YJ et al.. (2018) Discovery of a Novel Highly Selective Histamine H4 Receptor Antagonist for the Treatment of Atopic Dermatitis. J. Med. Chem., 61 (7): 2949-2961. [PMID:29579390]

18. Lim HD, Smits RA, Bakker RA, van Dam CM, de Esch IJ, Leurs R. (2006) Discovery of S-(2-guanidylethyl)-isothiourea (VUF 8430) as a potent nonimidazole histamine H4 receptor agonist. J Med Chem, 49: 6650-6651. [PMID:17154494]

19. Lim HD, van Rijn RM, Ling P, Bakker RA, Thurmond RL, Leurs R. (2005) Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist. J Pharmacol Exp Ther, 314: 1310-1321. [PMID:15947036]

20. Ling P, Ngo K, Nguyen S, Thurmond RL, Edwards JP, Karlsson L, Fung-Leung WP. (2004) Histamine H4 receptor mediates eosinophil chemotaxis with cell shape change and adhesion molecule upregulation. Br J Pharmacol, 142: 161-171. [PMID:15131002]

21. Lippert U, Artuc M, Grützkau A, Babina M, Guhl S, Haase I, Blaschke V, Zachmann K, Knosalla M, Middel P, Krüger-Krasagakis S, Henz BM. (2004) Human skin mast cells express H2 and H4, but not H3 receptors. J Invest Dermatol, 123: 116-123. [PMID:15191551]

22. Liu C, Ma X, Jiang X, Wilson SJ, Hofstra CL, Blevitt J, Pyati J, Li X, Chai W, Carruthers N, Lovenberg TW. (2001) Cloning and pharmacological characterization of a fourth histamine receptor (H(4)) expressed in bone marrow. Mol Pharmacol, 59: 420-426. [PMID:11179434]

23. Liu C, Wilson SJ, Kuei C, Lovenberg TW. (2001) Comparison of human, mouse, rat, and guinea pig histamine H4 receptors reveals substantial pharmacological species variation. J Pharmacol Exp Ther, 299: 121-130. [PMID:11561071]

24. Migalovich-Sheikhet H, Friedman S, Mankuta D, Levi-Schaffer F. (2012) Novel identified receptors on mast cells. Front Immunol, 3: 238. [PMID:22876248]

25. Morse KL, Behan J, Laz TM, West RE, Greenfeder SA, Anthes JC, Umland S, Wan Y, Hipkin RW, Gonsiorek W, Shin N, Gustafson EL, Qiao X, Wang S, Hedrick JA, Greene J, Bayne M, Monsma FJ. (2001) Cloning and characterization of a novel human histamine receptor. J Pharmacol Exp Ther, 296: 1058-1066. [PMID:11181941]

26. Nakamura T, Itadani H, Hidaka Y, Ohta M, Tanaka K. (2000) Molecular cloning and characterization of a new human histamine receptor, HH4R. Biochem Biophys Res Commun, 279: 615-620. [PMID:11118334]

27. Nakayama T, Kato Y, Hieshima K, Nagakubo D, Kunori Y, Fujisawa T, Yoshie O. (2004) Liver-expressed chemokine/CC chemokine ligand 16 attracts eosinophils by interacting with histamine H4 receptor. J Immunol, 173: 2078-2083. [PMID:15265943]

28. Nguyen T, Shapiro DA, George SR, Setola V, Lee DK, Cheng R, Rauser L, Lee SP, Lynch KR, Roth BL, O'Dowd BF. (2001) Discovery of a novel member of the histamine receptor family. Mol Pharmacol, 59: 427-433. [PMID:11179435]

29. O'Reilly M, Alpert R, Jenkinson S, Gladue RP, Foo S, Trim S, Peter B, Trevethick M, Fidock M. (2002) Identification of a histamine H4 receptor on human eosinophils--role in eosinophil chemotaxis. J. Recept. Signal Transduct. Res., 22 (1-4): 431-48. [PMID:12503632]

30. Oda T, Morikawa N, Saito Y, Masuho Y, Matsumoto S. (2000) Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes. J Biol Chem, 275: 36781-36786. [PMID:10973974]

31. Panula P, Chazot PL, Cowart M, Gutzmer R, Leurs R, Liu WL, Stark H, Thurmond RL, Haas HL. (2015) International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors. Pharmacol. Rev., 67 (3): 601-55. [PMID:26084539]

32. Parsons ME, Ganellin CR. (2006) Histamine and its receptors. Br. J. Pharmacol., 147 Suppl 1: S127-35. [PMID:16402096]

33. Sander LE, Lorentz A, Sellge G, Coëffier M, Neipp M, Veres T, Frieling T, Meier PN, Manns MP, Bischoff SC. (2006) Selective expression of histamine receptors H1R, H2R, and H4R, but not H3R, in the human intestinal tract. Gut, 55: 498-504. [PMID:16299042]

34. Savall BM, Chavez F, Tays K, Dunford PJ, Cowden JM, Hack MD, Wolin RL, Thurmond RL, Edwards JP. (2014) Discovery and SAR of 6-alkyl-2,4-diaminopyrimidines as histamine H₄ receptor antagonists. J. Med. Chem., 57 (6): 2429-39. [PMID:24495018]

35. Shin N, Coates E, Murgolo NJ, Morse KL, Bayne M, Strader CD, Monsma FJ. (2002) Molecular modeling and site-specific mutagenesis of the histamine-binding site of the histamine H4 receptor. Mol Pharmacol, 62: 38-47. [PMID:12065753]

36. Smits RA, Lim HD, Stegink B, Bakker RA, de Esch IJ, Leurs R. (2006) Characterization of the histamine H4 receptor binding site. Part 1. Synthesis and pharmacological evaluation of dibenzodiazepine derivatives. J. Med. Chem., 49 (15): 4512-6. [PMID:16854056]

37. Takeshita K, Bacon KB, Gantner F. (2004) Critical role of L-selectin and histamine H4 receptor in zymosan-induced neutrophil recruitment from the bone marrow: comparison with carrageenan. J Pharmacol Exp Ther, 310: 272-280. [PMID:14996947]

38. Terzioglu N, van Rijn RM, Bakker RA, de Esch IJ, Leurs R. (2004) Synthesis and structure-activity relationships of indole and benzimidazole piperazines as histamine H(4) receptor antagonists. Bioorg Med Chem Lett, 14: 5251-5256. [PMID:15454206]

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Paul Chazot, Hiroyuki Fukui, C. Robin Ganellin, Helmut L. Haas, Stephen J. Hill, Rebecca Hills, Roberto Levi, Walter Schunack, Jean-Charles Schwartz, Nigel P. Shankley, Henk Timmerman, J. Michael Young.
Histamine receptors: H4 receptor. Last modified on 04/04/2018. Accessed on 19/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=265.