Top ▲

H3 receptor

Click here for help

Target id: 264

Nomenclature: H3 receptor

Family: Histamine receptors

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 445 20q13.33 HRH3 histamine receptor H3 16,37
Mouse 7 445 2 102.62 cM Hrh3 histamine receptor H3 13,50
Rat 7 445 3q43 Hrh3 histamine receptor H3 36
Previous and Unofficial Names Click here for help
GPCR97 | H3R | HH3R
Database Links Click here for help
Specialist databases
GPCRDB hrh3_human (Hs), hrh3_mouse (Mm), hrh3_rat (Rn)
Other databases
Alphafold
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands Click here for help
histamine

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H](R)-α-methylhistamine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 9.2 pKd 35
pKd 9.2 (Kd 6x10-10 M) [35]
N-[3H]methylhistamine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Full agonist 9.1 pKd 35
pKd 9.1 [35]
N-[3H]methylhistamine Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Full agonist 9.1 pKd 36
pKd 9.1 [36]
N-[3H]α-methylhistamine Small molecule or natural product Ligand is labelled Ligand is radioactive Mm Full agonist 9.0 pKd 13
pKd 9.0 (Kd 1x10-9 M) [13]
[3H]histamine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Full agonist 8.0 pKd 35,43
pKd 8.0 [35,43]
iodoproxyfan Small molecule or natural product Hs Full agonist 10.0 pKi 58
pKi 10.0 [58]
immepip Small molecule or natural product Immunopharmacology Ligand Mm Full agonist 9.8 pKi 13
pKi 9.8 [13]
GSK-189254 Small molecule or natural product Hs Inverse agonist 9.7 pKi 39
pKi 9.7 (Ki 2x10-10 M) [39]
iodoproxyfan Small molecule or natural product Rn Full agonist 9.6 pKi 58
pKi 9.6 [58]
cipralisant Small molecule or natural product Rn Full agonist 9.5 pKi 58
pKi 9.5 [58]
imetit Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Rn Full agonist 9.0 – 9.7 pKi 36,41,58
pKi 9.0 – 9.7 [36,41,58]
imetit Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Full agonist 8.8 – 9.7 pKi 16,35-36,57-58
pKi 8.8 – 9.7 [16,35-36,57-58]
imetit Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Mm Full agonist 8.8 – 9.7 pKi 13,50
pKi 8.8 – 9.7 [13,50]
immepip Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Full agonist 8.8 – 9.7 pKi 16,31,35-36,58
pKi 8.8 – 9.7 [16,31,35-36,58]
immethridine Small molecule or natural product Hs Full agonist 9.1 pKi 30
pKi 9.1 [30]
N-α-methylhistamine Small molecule or natural product Mm Full agonist 9.0 pKi 13
pKi 9.0 [13]
methimepip Small molecule or natural product Click here for species-specific activity table Hs Full agonist 9.0 pKi 29
pKi 9.0 (Ki 1x10-9 M) [29]
N-methylhistamine Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.6 – 9.3 pKi 16,35-36
pKi 8.6 – 9.3 [16,35-36]
immepip Small molecule or natural product Immunopharmacology Ligand Rn Full agonist 8.8 – 8.9 pKi 36,58
pKi 8.8 – 8.9 [36,58]
N-methylhistamine Small molecule or natural product Click here for species-specific activity table Rn Full agonist 8.8 pKi 36
pKi 8.8 [36]
(R)-α-methylhistamine Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Full agonist 8.4 – 9.2 pKi 16,33,35-36,57-58
pKi 8.4 – 9.2 [16,33,35-36,57-58]
MK-0249 Small molecule or natural product Click here for species-specific activity table Hs Inverse agonist 8.8 pKi 42
pKi 8.8 (Ki 1.7x10-9 M) [42]
GR 175737 Small molecule or natural product Hs Partial agonist 8.6 pKi 58
pKi 8.6 [58]
cipralisant Small molecule or natural product Hs Full agonist 8.6 pKi 58
pKi 8.6 [58]
VUF 8328 Small molecule or natural product Hs Partial agonist 8.5 pKi 57
pKi 8.5 [57]
(R)-α-methylhistamine Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Mm Full agonist 8.4 pKi 13
pKi 8.4 [13]
imbutamine Small molecule or natural product Hs Full agonist 8.4 pKi 31
pKi 8.4 [31]
compound 3a [PMID: 18606542] Small molecule or natural product Hs Inverse agonist 8.4 pKi 49
pKi 8.4 (Ki 4x10-9 M) [49]
Description: Affinity measured in a saturation binding experiment using human H3 receptor-expressing CHO cells, and [3H]-(R)-α-methylhistamine as tracer.
(R)-α-methylhistamine Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Rn Full agonist 8.0 – 8.7 pKi 33,36,58
pKi 8.0 – 8.7 [33,36,58]
proxyfan Small molecule or natural product Mm Full agonist 8.2 – 8.5 pKi 50
pKi 8.2 – 8.5 [50]
GR 175737 Small molecule or natural product Rn Partial agonist 8.3 pKi 58
pKi 8.3 [58]
impentamine Small molecule or natural product Hs Full agonist 8.3 pKi 31
pKi 8.3 [31]
proxyfan Small molecule or natural product Hs Full agonist 8.3 pKi 58
pKi 8.3 [58]
proxyfan Small molecule or natural product Rn Full agonist 8.0 – 8.5 pKi 41,58
pKi 8.0 – 8.5 [41,58]
SUVN-G3031 Small molecule or natural product Hs Inverse agonist 8.1 pKi 44
pKi 8.1 (Ki 8.73x10-9 M) [44]
histamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 7.8 – 8.3 pKi 16,31,33,35-36,58
pKi 7.8 – 8.3 [16,31,33,35-36,58]
VUF 5207 Small molecule or natural product Hs Full agonist 7.8 pKi 57
pKi 7.8 [57]
(S)-α-methylhistamine Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.6 pKi 58
pKi 7.6 [58]
histamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Rn Full agonist 7.2 – 7.9 pKi 33,36,41
pKi 7.2 – 7.9 [33,36,41]
histamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Mm Full agonist 7.1 – 7.8 pKi 13,50
pKi 7.1 – 7.8 [13,50]
impromidine Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Partial agonist 7.2 pKi 35
pKi 7.2 [35]
(S)-α-methylhistamine Small molecule or natural product Rn Full agonist 6.6 pKi 58
pKi 6.6 [58]
ST-1006 Small molecule or natural product Click here for species-specific activity table Hs Agonist 6.3 pKi 45
pKi 6.3 [45]
dimaprit Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.1 pKi 35
pKi 6.1 [35]
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[123I]iodoproxyfan Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Antagonist 10.3 pKd 33
pKd 10.3 [33]
[123I]iodoproxyfan Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 10.2 pKd 33
pKd 10.2 (Kd 6.3x10-11 M) [33]
[125I]iodophenpropit Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Antagonist 9.2 pKd 28
pKd 9.2 (Kd 6x10-10 M) [28]
GSK334429 Small molecule or natural product Primary target of this compound Hs Antagonist 9.5 – 9.9 pKi 6,34
pKi 9.5 – 9.9 (Ki 3.2x10-10 – 1.3x10-10 M) [6,34]
clobenpropit Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Mm Antagonist 9.5 pKi 13
pKi 9.5 [13]
A-349821 Small molecule or natural product Click here for species-specific activity table Hs Inverse agonist 9.4 pKi 18
pKi 9.4 [18]
ABT-239 Small molecule or natural product Click here for species-specific activity table Hs Inverse agonist 9.4 pKi 19
pKi 9.4 [19]
clobenpropit Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Rn Antagonist 8.9 – 9.8 pKi 20,33,36,41,57-58
pKi 8.9 – 9.8 [20,33,36,41,57-58]
ciproxifan Small molecule or natural product Mm Antagonist 9.1 – 9.4 pKi 50
pKi 9.1 – 9.4 [50]
A-317920 Small molecule or natural product Rn Antagonist 9.2 pKi 18,20
pKi 9.2 [18,20]
JNJ-5207852 Small molecule or natural product Hs Antagonist 9.2 pKi 1
pKi 9.2 [1]
iodophenpropit Small molecule or natural product Rn Antagonist 8.8 – 9.1 pKi 57-58
pKi 8.8 – 9.1 [57-58]
clobenpropit Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 8.4 – 9.4 pKi 16,20,33,35-36,57-58
pKi 8.4 – 9.4 (Ki 3.9x10-9 – 3.9x10-10 M) [16,20,33,35-36,57-58]
ABT-239 Small molecule or natural product Rn Inverse agonist 8.9 pKi 19
pKi 8.9 [19]
ciproxifan Small molecule or natural product Rn Antagonist 8.4 – 9.3 pKi 18,20,33,41,58
pKi 8.4 – 9.3 [18,20,33,41,58]
A-349821 Small molecule or natural product Rn Inverse agonist 8.8 pKi 18
pKi 8.8 [18]
enerisant Small molecule or natural product Hs Inverse agonist 8.8 pKi 25
pKi 8.8 (Ki 1.65x10-9 M) [25]
Description: Determined using [3H]N-α-methylhistamine binding to the membranes of CHO-K1 cells expressing human recombinant H3 receptors.
thioperamide Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Mm Antagonist 8.6 – 8.8 pKi 50
pKi 8.6 – 8.8 [50]
FUB 349 Small molecule or natural product Hs Antagonist 8.7 pKi 33
pKi 8.7 [33]
PF-03654746 Small molecule or natural product Hs Antagonist 8.6 pKi 56
pKi 8.6 (Ki 2.3x10-9 M) [56]
proxyfan Small molecule or natural product Hs Antagonist 8.6 pKi 33
pKi 8.6 [33]
A-304121 Small molecule or natural product Rn Antagonist 8.6 pKi 18,20
pKi 8.6 [18,20]
proxyfan Small molecule or natural product Rn Antagonist 8.5 pKi 33
pKi 8.5 [33]
A331440 Small molecule or natural product Hs Antagonist 8.5 pKi 23
pKi 8.5 [23]
iodophenpropit Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.2 – 8.7 pKi 57-58
pKi 8.2 – 8.7 (Ki 6.31x10-9 – 1.99x10-9 M) [57-58]
pitolisant Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.1 – 8.6 pKi 45,61
pKi 8.1 – 8.6 (Ki 2.7x10-9 M) [45,61]
Description: Measured in a [125I]iodoproxyfan binding assay in cells exogenously expressing the human H3 receptor.
impentamine Small molecule or natural product Hs Antagonist 8.3 pKi 57
pKi 8.3 [57]
impentamine Small molecule or natural product Rn Antagonist 8.3 pKi 57
pKi 8.3 [57]
conessine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.3 pKi 45
pKi 8.3 [45]
thioperamide Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 7.7 – 8.8 pKi 18,20,33,36,41,57-58
pKi 7.7 – 8.8 [18,20,33,36,41,57-58]
MK-0249 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.2 pKi 45
pKi 8.2 [45]
enerisant Small molecule or natural product Rn Inverse agonist 8.1 pKi 25
pKi 8.1 (Ki 7.87x10-9 M) [25]
FUB 349 Small molecule or natural product Rn Antagonist 7.9 pKi 33
pKi 7.9 [33]
VUF 4904 Small molecule or natural product Hs Antagonist 7.9 pKi 57
pKi 7.9 [57]
VUF14862 Small molecule or natural product Hs Antagonist 7.7 pKi 24
pKi 7.7 (Ki 1.95x10-8 M) [24]
Description: Ki measured in the dark and compound in the trans configuration.
FUB 349 Small molecule or natural product Mm Antagonist 7.6 – 7.8 pKi 50
pKi 7.6 – 7.8 [50]
GT2394 Small molecule or natural product Rn Antagonist 7.7 pKi 58
pKi 7.7 [58]
UCL-2138 Small molecule or natural product Hs Antagonist 7.6 pKi 35
pKi 7.6 [35]
PF-03654746 Small molecule or natural product Mm Antagonist 7.4 pKi 56
pKi 7.4 (Ki 3.7x10-8 M) [56]
thioperamide Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.1 – 7.7 pKi 16,18,20,33,36,57-58
pKi 7.1 – 7.7 (Ki 7.94x10-8 – 1.99x10-8 M) Selective for H3/H4 compared to H1 and H3. [16,18,20,33,36,57-58]
VUF14738 Small molecule or natural product Hs Antagonist 7.3 pKi 24
pKi 7.3 (Ki 4.786x10-8 M) [24]
Description: Ki measured under UV illumination, and compound in cis configuration.
burimamide Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.3 pKi 57
pKi 7.3 [57]
JB 98064 Small molecule or natural product Hs Antagonist 7.3 pKi 58
pKi 7.3 [58]
burimamide Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.1 pKi 35,57
pKi 7.1 [35,57]
A-317920 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.0 pKi 18,20
pKi 7.0 [18,20]
JB 98064 Small molecule or natural product Rn Antagonist 7.0 pKi 58
pKi 7.0 [58]
ciproxifan Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.7 – 7.3 pKi 16,18,20,33,45,58
pKi 6.7 – 7.3 [16,18,20,33,45,58]
adriforant Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 6.7 pKi 45
pKi 6.7 [45]
FUB 465 Small molecule or natural product Rn Antagonist 6.4 – 6.9 pKi 41
pKi 6.4 – 6.9 [41]
GT2394 Small molecule or natural product Hs Antagonist 6.4 pKi 58
pKi 6.4 [58]
INCB-38579 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.4 pKi 45
pKi 6.4 [45]
A-304121 Small molecule or natural product Hs Antagonist 6.1 pKi 18,20
pKi 6.1 [18,20]
JNJ-39758979 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 6.0 pKi 45
pKi 6.0 (Ki 1x10-6 M) [45]
clozapine Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 5.8 pKi 36
pKi 5.8 [36]
View species-specific antagonist tables
Antagonist Comments
VUF 4904 is a neutral antagonist [57]. The affinity of VUF14738 decreases to 646 nM in the trans configuration adopted in the dark [24]. VUF14862 operates in the opposite direction, its affinity increases to 1.7 nM in the cis configuration adopted in the dark [24].
Immunopharmacology Comments
H3 receptor expression is low in peripheral tissues, but high in neuronal mast cells and eosinophils. It is not currently considered an important target in allergy.
Cell Type Associations
Immuno Cell Type:  Mast cells
Cell Ontology Term:   mast cell (CL:0000097)
Comment:  In humans, H3R expression is restricted to brain mast cells.
References:  21
Immuno Cell Type:  Granulocytes
Cell Ontology Term:   eosinophil (CL:0000771)
Comment:  Eosinophils express all four histamine receptor subtypes.
References:  22,40
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Adenylyl cyclase inhibition
References:  14-15
Tissue Distribution Click here for help
Brain: thalamus, caudate nucleus, putamen, cerebellum, amygdala, substantia nigra, hippocampus, hypothalamus, cerebral cortex.
Species:  Human
Technique:  Northern blotting and RT-PCR.
References:  16
Brain: thalamus, hypothalamus, hippocampus > cerebellum, brainstem.
Species:  Mouse
Technique:  Radioligand binding.
References:  27
Brain: cerebral cortex, basal ganglia, caudate putamen, nucleus accumbens, subthalamic nucleus, hypothalamus, thalamus, hippocampus, dentate gyrus, cerebellum.
Species:  Mouse
Technique:  in situ hybridisation.
References:  50
Brain: cerebral cortex, hippocampus, cerebellum, striatum, olfactory tubercle, substantia nigra, thalamus.
Species:  Mouse
Technique:  Immunohistochemistry.
References:  12
Brain: cerebral cortex, striatum, hypothalamus.
Species:  Mouse
Technique:  Southern blotting and RT-PCR.
References:  50
Embryo: lipoblasts of adipose tissue, tongue.
Adult: epithelial layer of the tongue, epithelial cells of hair follicles and epidermis, gastric mucosa of the stomach.
Species:  Rat
Technique:  in situ hybridisation.
References:  26
Skin, dorsal root ganglia, superior cervical ganglia, spinal cord.
Species:  Rat
Technique:  Immunohistochemistry.
References:  9
Brain: cerebral cortex, hippocampus, midbrain, hypothalamus, striatum, brainstem, cerebellum, olfactory tuberculum.
Species:  Rat
Technique:  Southern blotting and RT-PCR.
References:  41
Brain: cerebral cortex, thalamic nuclei, hippocampus, dentate gyrus, basal ganglia, substantia nigra, caudate putamen, nucleus accumbens, amygdala, thalamus, hypothalamus, brainstem, cerebellum.
Species:  Rat
Technique:  in situ hybridisation.
References:  47
Embryo: brain, spinal cord, spinal ganglia, tongue epithelium, salivary glands, respiratory epithelium, lung, stomach, intestine, skin, thymus, liver, adipose tissue.
Adult: brain, spinal cord, spinal ganglia, tongue epithelium, stomach, intestine, skin, thymus.
Species:  Rat
Technique:  in situ hybridisation.
References:  26
Cochlea.
Species:  Rat
Technique:  RT-PCR.
References:  3
Embryo: adipose tissue, liver.
Adult: brain.
Species:  Rat
Technique:  RT-PCR and Southern blotting.
References:  26
Expression Datasets Click here for help

Show »

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]

There should be a chart of expression data here, you may need to enable JavaScript!
Functional Assays Click here for help
Measurement of Ca2+ levels in CHO cells transfected with the human H3 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Ca2+ mobilisation.
References:  16
Measurement of cAMP levels in SK-N-MC cells transfected with the rat H3 receptor.
Species:  Rat
Tissue:  SK-N-MC cells.
Response measured:  Inhibition of cAMP accumulation.
References:  36,57
Measurement of Ca2+ levels in HEK 293 cells transfected with the mouse H3 receptor.
Species:  Mouse
Tissue:  HEK 293 cells.
Response measured:  Ca2+ mobilisation.
References:  13
Measurement of cAMP levels in SK-N-MC cells transfected with the human H3 receptor.
Species:  Human
Tissue:  SK-N-MC cells.
Response measured:  Inhibition of cAMP accumulation.
References:  57
Measurement of MAP kinase activation in COS-7 cells transfected with the rat H3 receptor.
Species:  Rat
Tissue:  COS-7 cells.
Response measured:  Activation of p44/p42 MAPK.
References:  17
Physiological Functions Click here for help
Inhibition of substantia nigra pars reticulata (SNr) inhibitory projection neuron firing frequency (via cell hyperpolarisation).
The balance between this effect and the opposing effect of H1 and H2 receptors may contribute to movement control.
Species:  Mouse
Tissue:  Coronal midbrain slices.
References:  60
Inhibition of gastric acid secretion.
Species:  Rat
Tissue:  In vivo.
References:  5
Inhibition of serotonin release in the substantia nigra pars reticulata (SNr).
Species:  Rat
Tissue:  Midbrain slices.
References:  52
Inhibition of acetylcholine release.
Species:  Rat
Tissue:  Isolated stomach.
References:  59
Inhibition of glutamate release.
Species:  Rat
Tissue:  Dentate gyrus.
References:  7
Inhibition of cholinergic transmission.
Role in consolidation of fear conditioning.
Species:  Rat
Tissue:  In vivo.
References:  8,46
Vasoconstriction.
Species:  Human
Tissue:  Turbinate mucosa strips.
References:  55
Regulation of food intake and body weight.
Species:  Rat
Tissue:  In vivo.
References:  38
Activation of spinal H3 receptors inhibits mechanical nociception.
Species:  Human
Tissue:  In vivo.
References:  11
Autoreceptor: inhibition of histamine release.
Species:  Rat
Tissue:  Cerebral cortex.
References:  2
Inhibition of chemical and mechanical nociception.
Species:  Rat
Tissue:  In vivo.
References:  10
Physiological Consequences of Altering Gene Expression Click here for help
H3 receptor knockout mice exhibit normal circadian rhythmicity, but a decrease in locomotion, wheel-running behaviour and body temperature during the dark phase.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  54
H3 receptor knockout mice exhibit a mild obese phenotype, suggesting the H3 receptor may have a role in energy homeostasis.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  51
Sympathetic nerve endings from hearts from H3 receptor knockout mice exhibit an increase in basal noradrenaline release compared to hearts from wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  32
H3 receptor knockout mice exhibit increased spatial learning and memory as well as reduced levels of anxiety.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  48
H3 receptor knockout mice exhibit hyperphagia and late-onset obesity.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  53
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Hrh3tm1Twl Hrh3tm1Twl/Hrh3tm1Twl
involves: 129X1/SvJ * C57BL/6J
MGI:2139279  MP:0001362 abnormal anxiety-related response PMID: 12130692 
Hrh3tm1Twl Hrh3tm1Twl/Hrh3tm1Twl
B6.129X1-Hrh3
MGI:2139279  MP:0005167 abnormal blood-brain barrier function PMID: 17548817 
Hrh3tm1Twl Hrh3tm1Twl/Hrh3tm1Twl
involves: 129X1/SvJ * C57BL/6J
MGI:2139279  MP:0001777 abnormal body temperature regulation PMID: 12130692 
Hrh3tm1Twl Hrh3tm1Twl/Hrh3tm1Twl
involves: 129X1/SvJ
MGI:2139279  MP:0001544 abnormal cardiovascular system physiology PMID: 12527809 
Hrh3tm1Kot Hrh3tm1Kot/Hrh3tm1Kot
involves: 129X1/SvJ * C57BL/6N
MGI:2139279  MP:0005450 abnormal energy expenditure PMID: 12488429 
Hrh3tm1Twl Hrh3tm1Twl/Hrh3tm1Twl
involves: 129X1/SvJ * C57BL/6J
MGI:2139279  MP:0003953 abnormal hormone level PMID: 15078574 
Hrh3tm1Twl Hrh3tm1Twl/Hrh3tm1Twl
involves: 129X1/SvJ * C57BL/6J
MGI:2139279  MP:0003313 abnormal locomotor activation PMID: 12130692 
Hrh3tm1Twl Hrh3tm1Twl/Hrh3tm1Twl
involves: 129X1/SvJ * C57BL/6J
MGI:2139279  MP:0003633 abnormal nervous system physiology PMID: 12130692 
Hrh3tm1Twl Hrh3tm1Twl/Hrh3tm1Twl
involves: 129X1/SvJ * C57BL/6J
MGI:2139279  MP:0001463 abnormal spatial learning PMID: 15078574 
Hrh3tm1Twl Hrh3tm1Twl/Hrh3tm1Twl
involves: 129X1/SvJ
MGI:2139279  MP:0005447 abnormal synaptic norepinephrine release PMID: 12527809 
Hrh3tm1Twl Hrh3tm1Twl/Hrh3tm1Twl
involves: 129X1/SvJ * C57BL/6J
MGI:2139279  MP:0001364 decreased anxiety-related response PMID: 15078574 
Hrh3tm1Kot Hrh3tm1Kot/Hrh3tm1Kot
involves: 129X1/SvJ * C57BL/6N
MGI:2139279  MP:0005534 decreased body temperature PMID: 12488429 
Hrh3tm1Kot Hrh3tm1Kot/Hrh3tm1Kot
involves: 129X1/SvJ * C57BL/6N
MGI:2139279  MP:0005290 decreased oxygen consumption PMID: 12488429 
Hrh3tm1Kot Hrh3tm1Kot/Hrh3tm1Kot
involves: 129X1/SvJ * C57BL/6N
MGI:2139279  MP:0001402 hypoactivity PMID: 12488429 
Hrh3tm1Twl Hrh3tm1Twl/Hrh3tm1Twl
involves: 129X1/SvJ * C57BL/6J
MGI:2139279  MP:0001363 increased anxiety-related response PMID: 15078574 
Hrh3tm1Kot Hrh3tm1Kot/Hrh3tm1Kot
involves: 129X1/SvJ * C57BL/6N
MGI:2139279  MP:0002079 increased circulating insulin level PMID: 12488429 
Hrh3tm1Kot Hrh3tm1Kot/Hrh3tm1Kot
involves: 129X1/SvJ * C57BL/6N
MGI:2139279  MP:0005669 increased circulating leptin level PMID: 12488429 
Hrh3tm1Twl Hrh3tm1Twl/Hrh3tm1Twl
B6.129X1-Hrh3
MGI:2139279  MP:0004799 increased susceptibility to experimental autoimmune encephalomyelitis PMID: 17548817 
Hrh3tm1Kot Hrh3tm1Kot/Hrh3tm1Kot
involves: 129X1/SvJ * C57BL/6N
MGI:2139279  MP:0005455 increased susceptibility to weight gain PMID: 12488429 
Hrh3tm1Kot Hrh3tm1Kot/Hrh3tm1Kot
involves: 129X1/SvJ * C57BL/6N
MGI:2139279  MP:0010024 increased total body fat amount PMID: 12488429 
Hrh3tm1Kot Hrh3tm1Kot/Hrh3tm1Kot
involves: 129X1/SvJ * C57BL/6N
MGI:2139279  MP:0005331 insulin resistance PMID: 12488429 
Hrh3tm1Kot Hrh3tm1Kot/Hrh3tm1Kot
involves: 129X1/SvJ * C57BL/6N
MGI:2139279  MP:0001433 polyphagia PMID: 12488429 
Biologically Significant Variants Click here for help
Type:  Splice variants
Species:  Human
Description:  Expression of human H3 receptor splice variants in CHO cells show that a deletion in the 2nd transmembrane domain alters ligand binding and deletions in the 3rd intracellular loop result in signal transduction being abolished.
References:  16
Type:  Splice variants
Species:  Rat
Description:  Various H3 receptor splice variants have been reported to exist rat tissues. When expressed in in CHO and COS-7 cells, some have altered pharmacological properties or cell surface trafficking.
References:  4,41

References

Show »

1. Apodaca R, Dvorak CA, Xiao W, Barbier AJ, Boggs JD, Wilson SJ, Lovenberg TW, Carruthers NI. (2003) A new class of diamine-based human histamine H3 receptor antagonists: 4-(aminoalkoxy)benzylamines. J Med Chem, 46 (18): 3938-44. [PMID:12930154]

2. Arrang JM, Garbarg M, Schwartz JC. (1983) Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor. Nature, 302 (5911): 832-7. [PMID:6188956]

3. Azuma H, Sawada S, Takeuchi S, Higashiyama K, Kakigi A, Takeda T. (2003) Expression of mRNA encoding the H1, H2, and H3 histamine receptors in the rat cochlea. Neuroreport, 14 (3): 423-5. [PMID:12634496]

4. Bakker RA, Lozada AF, van Marle A, Shenton FC, Drutel G, Karlstedt K, Hoffmann M, Lintunen M, Yamamoto Y, van Rijn RM et al.. (2006) Discovery of naturally occurring splice variants of the rat histamine H3 receptor that act as dominant-negative isoforms. Mol Pharmacol, 69 (4): 1194-206. [PMID:16415177]

5. Barocelli E, Ballabeni V, Chiavarini M, Impicciatore M. (1995) R-alpha-methylhistamine-induced inhibition of gastric acid secretion in pylorus-ligated rats via central histamine H3 receptors. Br J Pharmacol, 115 (7): 1326-30. [PMID:7582564]

6. Berlin M, Boyce CW, Ruiz Mde L. (2011) Histamine H3 receptor as a drug discovery target. J Med Chem, 54 (1): 26-53. [PMID:21062081]

7. Brown RE, Haas HL. (1999) On the mechanism of histaminergic inhibition of glutamate release in the rat dentate gyrus. J Physiol (Lond.), 515 ( Pt 3): 777-86. [PMID:10066904]

8. Cangioli I, Baldi E, Mannaioni PF, Bucherelli C, Blandina P, Passani MB. (2002) Activation of histaminergic H3 receptors in the rat basolateral amygdala improves expression of fear memory and enhances acetylcholine release. Eur J Neurosci, 16 (3): 521-8. [PMID:12193196]

9. Cannon KE, Chazot PL, Hann V, Shenton F, Hough LB, Rice FL. (2007) Immunohistochemical localization of histamine H3 receptors in rodent skin, dorsal root ganglia, superior cervical ganglia, and spinal cord: potential antinociceptive targets. Pain, 129 (1-2): 76-92. [PMID:17134835]

10. Cannon KE, Hough LB. (2005) Inhibition of chemical and low-intensity mechanical nociception by activation of histamine H3 receptors. J Pain, 6 (3): 193-200. [PMID:15772913]

11. Cannon KE, Nalwalk JW, Stadel R, Ge P, Lawson D, Silos-Santiago I, Hough LB. (2003) Activation of spinal histamine H3 receptors inhibits mechanical nociception. Eur J Pharmacol, 470 (3): 139-47. [PMID:12798951]

12. Chazot PL, Hann V, Wilson C, Lees G, Thompson CL. (2001) Immunological identification of the mammalian H3 histamine receptor in the mouse brain. Neuroreport, 12 (2): 259-62. [PMID:11209931]

13. Chen J, Liu C, Lovenberg TW. (2003) Molecular and pharmacological characterization of the mouse histamine H3 receptor. Eur J Pharmacol, 467 (1-3): 57-65. [PMID:12706455]

14. Clark EA, Hill SJ. (1996) Sensitivity of histamine H3 receptor agonist-stimulated [35S]GTP gamma[S] binding to pertussis toxin. Eur J Pharmacol, 296 (2): 223-5. [PMID:8838460]

15. Clark MA, Korte A, Egan RW. (1993) Guanine nucleotides and pertussis toxin reduce the affinity of histamine H3 receptors on AtT-20 cells. Agents Actions, 40 (3-4): 129-34. [PMID:8023737]

16. Cogé F, Guénin SP, Audinot V, Renouard-Try A, Beauverger P, Macia C, Ouvry C, Nagel N, Rique H, Boutin JA et al.. (2001) Genomic organization and characterization of splice variants of the human histamine H3 receptor. Biochem J, 355 (Pt 2): 279-88. [PMID:11284713]

17. Drutel G, Peitsaro N, Karlstedt K, Wieland K, Smit MJ, Timmerman H, Panula P, Leurs R. (2001) Identification of rat H3 receptor isoforms with different brain expression and signaling properties. Mol Pharmacol, 59 (1): 1-8. [PMID:11125017]

18. Esbenshade TA, Fox GB, Krueger KM, Baranowski JL, Miller TR, Kang CH, Denny LI, Witte DG, Yao BB, Pan JB et al.. (2004) Pharmacological and behavioral properties of A-349821, a selective and potent human histamine H3 receptor antagonist. Biochem Pharmacol, 68 (5): 933-45. [PMID:15294456]

19. Esbenshade TA, Fox GB, Krueger KM, Miller TR, Kang CH, Denny LI, Witte DG, Yao BB, Pan L, Wetter J et al.. (2005) Pharmacological properties of ABT-239 [4-(2-{2-[(2R)-2-Methylpyrrolidinyl]ethyl}-benzofuran-5-yl)benzonitrile]: I. Potent and selective histamine H3 receptor antagonist with drug-like properties. J Pharmacol Exp Ther, 313 (1): 165-75. [PMID:15608078]

20. Esbenshade TA, Krueger KM, Miller TR, Kang CH, Denny LI, Witte DG, Yao BB, Fox GB, Faghih R, Bennani YL et al.. (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 (3): 887-96. [PMID:12606603]

21. 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]

22. 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]

23. Hancock AA, Bennani YL, Bush EN, Esbenshade TA, Faghih R, Fox GB, Jacobson P, Knourek-Segel V, Krueger KM, Nuss ME et al.. (2004) Antiobesity effects of A-331440, a novel non-imidazole histamine H3 receptor antagonist. Eur J Pharmacol, 487 (1-3): 183-97. [PMID:15033391]

24. Hauwert NJ, Mocking TAM, Da Costa Pereira D, Kooistra AJ, Wijnen LM, Vreeker GCM, Verweij EWE, De Boer AH, Smit MJ, De Graaf C et al.. (2018) Synthesis and Characterization of a Bidirectional Photoswitchable Antagonist Toolbox for Real-Time GPCR Photopharmacology. J Am Chem Soc, 140 (12): 4232-4243. [PMID:29470065]

25. Hino N, Marumo T, Kotani M, Shimazaki T, Kaku-Fukumoto A, Hikichi H, Karasawa JI, Tomishima Y, Komiyama H, Tatsuda E et al.. (2020) A Novel Potent and Selective Histamine H3 Receptor Antagonist Enerisant: In Vitro Profiles, In Vivo Receptor Occupancy, and Wake-Promoting and Procognitive Effects in Rodents. J Pharmacol Exp Ther, 375 (2): 276-285. DOI: 10.1124/jpet.120.000185 [PMID:32862143]

26. Héron A, Rouleau A, Cochois V, Pillot C, Schwartz JC, Arrang JM. (2001) Expression analysis of the histamine H(3) receptor in developing rat tissues. Mech Dev, 105 (1-2): 167-73. [PMID:11429293]

27. Jansen FP, Mochizuki T, Maeyama K, Leurs R, Timmerman H. (2000) Characterization of histamine H3 receptors in mouse brain using the H3 antagonist [125I]iodophenpropit. Naunyn Schmiedebergs Arch Pharmacol, 362 (1): 60-7. [PMID:10935534]

28. Jansen FP, Wu TS, Voss HP, Steinbusch HW, Vollinga RC, Rademaker B, Bast A, Timmerman H. (1994) Characterization of the binding of the first selective radiolabelled histamine H3-receptor antagonist, [125I]-iodophenpropit, to rat brain. Br J Pharmacol, 113 (2): 355-62.