Histamine GPCR Family Subtypes and Products

What Are Histamine Receptors?

Histamine receptors are a family of G protein-coupled receptors (GPCRs) comprised of 4 receptors: H1, H2, H3, and H4. Histamine receptors play a large role in the inflammatory process, itching, allergy-related asthma, muscle constriction, and gastric acid secretion. Antihistamines (specific to only H1 receptors) and other histamine receptor antagonists are commonly used as allergy medications and antacids.

Histamine Receptor Information

Clickable Text Interaction





Histamine H1 receptor (H1 or HRH1) is a subclass of histamine receptors. It mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, and neurotransmission in the central nervous system. Antihistamines including H1 receptor antagonists are among the most frequently used pharmacologic agents because of a high incident rate of upper respiratory allergies. Clinical and laboratory evidence on histamine and its actions suggests that it has a pathophysiologic role in asthma. These findings have renewed interest in the potential therapeutic role of H1-receptor antagonists, such as, fexofenadine, which has been investigated as potential therapeutic targets for this disease.

H2 receptors are positively coupled to adenylate cyclase via Gs. It increases the intracellular Ca2+ concentrations and release Ca2+ from intracellular stores by coupling to Gq. H2 receptors have been found to be located in a variety of tissues, including the brain, gastric cells, and cardiac tissue. Histamine H2 receptors have a potent effect on gastric acid secretion, and the inhibition of this secretory process by H2 receptor antagonists has provided evidence for an important physiological role of histamine in the regulation of gastric secretion. It also regulates gastrointestinal motility and intestinal secretion and is thought to be involved in regulating cell growth and differentiation. It has also been demonstrated to control the relaxation of smooth muscles.

The histamine receptor H3 was initially recognized as an autoreceptor controlling histamine synthesis and release in the brain. The inhibition mediated by H3 autoreceptors constitutes a major regulatory mechanism of histaminergic neurons in vivo. Functional and localization studies have shown that H3 receptors are also present on perikarya, dendrites and projections of many other neurons in brain and peripheral tissues. The histamine receptor H3 has been found to prevent oxidative stress and alleviate schizophrenic symptoms, particularly the negative symptoms and cognitive deficits.

The histamine receptor H4 has been shown to have a role in chemotaxis and mediator release in a variety of immune cells, such as mast cells, eosinophils, dendritic cells, and T cells. The development of potent H4 receptor antagonists has great potential to open up the pathway for new therapeutic treatments in chronic inflammatory diseases, such as bronchial asthma, allergic gastrointestinal disease, and atopic dermatitis.

Histamine Cell Lines

Receptor FamilyReceptorSpeciesParentalStable Cell Lines Division-Arrested Cells Membranes
H3humanHEK293T Gαqi5CG1029DCG1029MCG1029
H4humanHEK293T Gαqi5CG1030DCG1030MCG1030
H4humanHEK293T β-Arrestin2CA1030BA2DCA1030BA2MCA1030BA2
H4mouseHEK293T Gαqi5CGm1030DCGm1030MCGm1030