Histamine Family Related Drug Discovery Products
Creative Biolabs has the assays you can rely on for high throughput screening, lead optimization, characterizing and discovering targets, and uncovering the complexity of disease pathways. We can offer membrane protein in vitro assay kits that save valuable laboratory time and is ideal for high throughput screening.
Membrane protein stable cell lines are widely used in many areas of biomedical research. Creative Biolabs can offer membrane protein stable cell lines to stablish in vitro models for High Throughput Screening.
Creative Biolabs offers high-quality, innovative tools to help research groups accelerate membrane protein drug discovery. They can be found by targets. If there is no product that meets your needs, please contact us.
The biogenic amine histamine has wide-ranging effects on a variety of cell types, including crucial immune cells including T and B lymphocytes, natural killer cells, epithelial cells, and antigen-presenting cells. With varied actions based on receptor subtypes and their variable expression, histamine and its four receptors comprise a sophisticated immunoregulatory system. These are affected by the stage of cell differentiation as well as microenvironmental factors, which results in the selective recruitment of effector cells into tissue sites along with effects on cellular maturation, activation, polarization, and effector functions that result in tolerogenic or proinflammatory responses.
Fig.1 Histamine receptors. (O’Mahony, 2011)
Creative Biolabs offers high-quality histamine family assays and products to help research groups accelerate drug discovery:
Overview of Histamine Family
There are 487 amino acids in the human Gq/11-coupled HRH1. Many cells, including hepatocytes, chondrocytes, nerve cells, endothelial cells, DCs, monocytes, neutrophils, T cells, and B cells, express the HRH1gene. The transmembrane domains 3 and 5 bind to histamine. Inositol-1,4,5-triphosphate (IP3) and diacylglycerol are produced as a result of the activation of the HRH1-coupled Gq/11, which also results in a rise in intracellular calcium. Nitric oxide generation is explained by an increase in intracellular calcium, while cyclic AMP is enhanced by the release of arachidonic acid from phospholipids.
The 359 amino acid long human HRH2 protein activates c-Fos, c-Jun PKC, and p70S6 kinase via different GTP-dependent processes and is connected to both the adenylate cyclase and phosphoinositide second messenger systems. H2R is expressed in various cell types. Research in many animal species and human cells have shown that the HRH2 -dependent effects of histamine are predominantly dominated by the inhibition of the cellular characteristics by cAMP production. HRH2 is connected to the phosphoinositide and adenylate cyclase second messenger systems through several GTP-dependent pathways.
The pre-synaptic receptors known as H3R were first discovered in the central and peripheral nervous systems to regulate the release of histamine and other neurotransmitters. Gi/o of G-proteins is required for HR3 signal transduction, which inhibits cAMP synthesis, causes Ca21 to accumulate, and activates the mitogen-activated protein kinase (MAPK) pathway. It affects inflammation, energy homeostasis, sleep-wake status, and cognition. It is a pre-synaptic autoreceptor that regulates histamine synthesis and release.
Human HR4 and HR3 are 37–43% homologous. Similar to HR3, HR4 also inhibits forskolin-induced cAMP formation when it is functionally coupled to Gi/o. When it is activated, adenylyl cyclase and downstream cAMP-responsive elements (CRE) are inhibited, MAPK and phospholipase C are activated, and Ca21 is mobilized. In the bone marrow, peripheral haematopoietic cells, neutrophils, eosinophils, and T cells, HR4 is highly expressed, but it is only moderately expressed in the spleen, thymus, lung, small intestine, colon, and heart.
Fig.2 Histamine regulates monocytes, dendritic cells, T cells and B cells. (Jutel, 2009)
References
- O’Mahony, L.; et al. Regulation of the immune response and inflammation by histamine and histamine receptors. Journal of Allergy and Clinical Immunology. 2011, 128(6): 1153-1162.
- Jutel, M.; et al. Histamine, histamine receptors and their role in immune pathology. Clinical & Experimental Allergy. 2009, 39(12): 1786-1800.
