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Histamine receptors
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	H1
	H2
	H3
	H4

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H₂

Structural Information class A G protein-coupled receptor Species TM AA Chromosomal Location Gene Name Reference Human 7 359 5q35.2 HRH2 70 Rat 7 358 17p14 Hrh2 69 Mouse 7 358 13 B1 Hrh2 71

Contents: Structural Information Database Links Agonists Antagonists Transduction Mechanisms Tissue Distribution Functional Assays Physiological Functions Physiological Consequences of Altering Gene Expression Biologically Significant Variants

Database Links
ChEMBL Target	102 (Hs), 11297 (Mm), 11298 (Rn)
Ensembl	ENSG00000113749 (Hs), ENSMUSG00000034987 (Mm), ENSRNOG00000018260 (Rn)
Entrez Gene	3274 (Hs), 15466 (Mm), 25461 (Rn)
GeneCards	HRH2 (Hs)
HomoloGene	40613 (Hs)
OMIM	142703 (Hs)
PharmGKB Gene	PA29457 (Hs)
Protein Ontology (PRO)	PRO:000001423 (Hs)
RefSeq Nucleotide	NM_022304 (Hs), NM_008286 (Mm), NM_012965 (Rn)
RefSeq Protein	NP_071640 (Hs), NP_032312 (Mm), NP_037097 (Rn)
UniGene Hs.	247885 (Hs)
UniProt	P25021 (Hs), P97292 (Mm), P25102 (Rn)
Wikipedia	H2

Search for 3D structures on the PDB
Search using keywords: Histamine receptors H2	Search using accession numbers: P25102 || P25021 || P97292

Agonists
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Affinity Units Reference impromidine Hs Full agonist 7.2 pKi 24 arpromidine Hs Full agonist 6.3 – 8.0 pKi 24 UR-PG136 Hs Full agonist 7.0 pKi 24 UR-PG146 Hs Full agonist 6.0 pKi 24 histamine Rn Full agonist 3.8 pKi 98 burimamide Hs Full agonist 5.6 – 5.7 pEC50 97
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 [125I]aminopotentidine Rn Antagonist 8.7 pKd 73 iodoaminopotentidine Rn Antagonist 9.2 pKi 98 tiotidine Rn Antagonist 7.5 pKi 98 ranitidine Rn Antagonist 6.2 pKi 98 cimetidine Rn Antagonist 5.9 pKi 98 metiamide Rn Antagonist 5.8 pKi 98 burimamide Rn Antagonist 5.5 pKi 99 ABT-239 Hs Inverse agonist 5.2 pKi 68 clobenpropit Hs Antagonist 5.2 pKi 66
View species-specific antagonist tables
Antagonist Comments
Nizatidine is a H2 antagonist clinically in use to block histamine-induced gastric acid secretion [72].

Primary Transduction Mechanisms
Transducer	Effector/Response
Gq/G11 family	Phospholipase C stimulation
References:  73-74

Secondary Transduction Mechanisms
Transducer	Effector/Response
Gs family	Adenylate cyclase stimulation
References:  73-74

Tissue Distribution
Brain: cerebrum. Heart: myocardium (atrium and ventricle). Species:  Rat Technique:  Northern and Western blotting. References:  30
Brain: cerebrum. Heart: myocardium (atrium and ventricle). Species:  Human Technique:  Northern and Western blotting. References:  30
Cochlea. Species:  Rat Technique:  RT-PCR. References:  34
Brain: caudate and putamen nuclei, external layers of cerebral cortex > hippocampal formation > dentate nucleus of cerebellum. Species:  Human Technique:  in situ hybridisation. References:  85
Mast cells. Species:  Mouse Technique:  RT-PCR. References:  37
Mast cells. Species:  Human Technique:  RT-PCR. References:  86
Gastrointestinal tract. Species:  Human Technique:  qRT-PCR and immunohistochemistry. References:  39

Functional Assays
Measurement of IP levels in COS-7 cells transfected with the rat H2 receptor. Species:  Rat Tissue:  COS-7 cells. Response measured:  Stimulation of IP formation. References:  73
Measurment of cAMP levels in COS-7 cells transfected with the rat H2 receptor. Species:  Rat Tissue:  COS-7 cells. Response measured:  Stimulation of cAMP accumulation. References:  73
Measurement of Ca2+ levels in primary cultured human uterine arterial endothelial (HUAEC) cells endogenously expressing the H2 receptor. Species:  Human Tissue:  HUAEC cells. Response measured:  Increase in Ca2+ concentration. References:  79
Measurement of cAMP levels in human neutrophils endogenously expressing the H2 receptor. Species:  Human Tissue:  Neutrophils. Response measured:  Stimulation of cAMP accumulation. References:  80
Measurement of cAMP levels in human promyelocytic leukemic HL-60 cells endogenously expressing the H2 receptor. Species:  Human Tissue:  HL-60 cells. Response measured:  Stimulation of cAMP accumulation. References:  81-82
Measurement of Ca2+ levels in human HL-60 cells endogenously expressing the H2 receptor. Species:  Human Tissue:  HL-60 cells. Response measured:  Ca2+ mobilisation from intracellular stores. References:  74
Measurement of cAMP levels in mast cells endogenously expressing the H2 receptor. Species:  Mouse Tissue:  Mast cells. Response measured:  Stimulation of cAMP accumulation. References:  37
Measurement of cAMP levels in CHO cells transfected with the human H2 receptor. Species:  Human Tissue:  CHO cells. Response measured:  cAMP accumulation. References:  83-84

Physiological Functions
Endothelium-independent vasodilation via smooth muscle H2 receptors. Species:  Rat Tissue:  Mesenteric vascular beds. References:  55
Relaxation of smooth muscle. Species:  Human Tissue:  Isolated uterine strips. References:  60
Inhibition of neutrophil activation. Species:  Human Tissue:  Neutrophils. References:  74
Inhibition of neutrophil chemotaxis and T-lymphocyte proliferation. Species:  Human Tissue:  In vivo. References:  82
Stimulation of gastric acid secretion. Species:  Rat Tissue:  In vivo. References:  87-91
Stimulation of gastric acid secretion. Species:  Human Tissue:  In vivo. References:  92-94
Relaxation of smooth muscle. Species:  Rat Tissue:  Isolated uterine strips. References:  95
Relaxation of smooth muscle. Species:  Rat Tissue:  Isolated stomach fundus. References:  61
Increase in substantia nigra pars reticulata (SNr) inhibitory projection neuron firing frequency (via cell depolarisation). The balance between the effect of H1 and H2 receptors and the opposing effect of H3 receptors may contribute to movement control. Species:  Mouse Tissue:  Coronal midbrain slices. References:  62
Depolarisation of CA3 pyramidal cells. Species:  Mouse Tissue:  Hippocampal slices. References:  96
Regulation of cytokine production. Species:  Mouse Tissue:  CD4+ and CD8+ T cells. References:  21

Physiological Consequences of Altering Gene Expression
H2 receptor knockout mice exhibit attenuation of the histamine-induced inhibition of the development of liver injury seen in wild-type mice. Species:  Mouse Tissue:  Technique:  Gene targeting in embryonic stem cells. References:  77
H2 receptor knockout mice develop normally with normal basal gastric acid levels. However they exhibit hypertrophy of gastric mucosa and an increase in the number of parietal and enterochromaffin-like (ECL) cells. Neither histamine nor gastrin stimulated gastric acid secretion in the knockout mice. Species:  Mouse Tissue:  Technique:  Gene targeting in embryonic stem cells. References:  75
H2 receptor knockout mice exhibit an increase in stomach weight, enlarged gastric folds with cystic dilatation, hypergastrinemia, hypoalbuminemia, an increase in mucus secretion and overexpression of mucosal TGFα. These symptoms resemble Menetrier's disease. Species:  Mouse Tissue:  Technique:  Gene targeting in embryonic stem cells. References:  76
CD4+ T cells from H2 receptor knockout mice exhibit a decrease in the release of IL-2 and IL-10, and increase in IL-4 release. CD8+ T cells from H2 receptor knockout mice also exhibit a decrease in the release of IL-2 and IL-10, as well as an increase in IFN-γ release. Species:  Mouse Tissue:  Technique:  Gene targeting in embryonic stem cells. References:  21
H1 receptor knockout mice exhibit enhanced antinociception by administration of orexin-A, compared to wild-type mice following administration of orexin-A. Species:  Mouse Tissue:  Technique:  Gene targeting in embryonic stem cells. References:  22

Biologically Significant Variants
A 649 A -> G substitution may be linked to schizophrenia. Type:  Single nucleotide polymorphism. Species:  Human References:  78

To cite this receptor data page, please use the following:

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: H₂. Last modified on 2010-06-30. Accessed on 2010-09-09. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=263.

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