Histamine subtypes

Hough LB (2001) Genomics meets histamine receptors new subtypes, new receptors. Mol Pharmacol 59 415-419... 

Schaefer U, Schneider A, Rixen D, Neugebauer E (1998) Neutrophil adhesion to histamine stimulated cultured endothelial cells is primarily mediated via activation of phospholipase C and nitric oxide synthase isozymes. Inflamm Res 47(6) 256-264 Schaefer U, Schmitz V, Schneider A, Neugebauer E (1999) Histamine induced homologous and heterologous regulation of histamine receptor subtype mRNA expression in cultured endothelial ceUs. Shock 12(4) 309-315... 

Histamine produces its pharmacological actions by three subtypes of receptors the postsynaptic Hi and H2 receptors and the presynaptic H3 receptor. The H3 receptor is mainly located in the central nervous system (CNS), where it acts as an inhibitory autoreceptor in the central histaminergic neuronal pathways [176]. A number of therapeutic applications have been proposed for selective H3 receptor antagonists, including several CNS disorders such as Alzheimer s disease. Attention Deficit Hyperactivity Disorder, Schizophrenia, or for enhancing memory or obesity control. 

Clapham, J. Kilpatrick, G. J. (1992). Histamine H3 receptors modulate the release of [3H]-acetylcholine from slices of rat entorhinal cortex evidence for the possible existence of H3 receptor subtypes. Br. ]. Pharmacol. 107,... 

Currently, three subtypes of histamine receptors are proposed and H2 receptors are found in peripheral tissues and the central nervous system (CNS), and receptors are found in the CNS. The second messenger pathway that mediates Hrreceptor stimulation is... 

Histamine induces intracellular Ca " flux, actin polymerization, and chemotaxis in immature DCs due to stimulation of HRl and HR3 subtypes. Maturation of DCs results in loss of these responses. In maturing DCs, however, histamine dose-dependently enhances intracellular cAMP levels and stimulates IL-10 secretion, while inhibiting production of IL-12 via HR2 [16]. Interestingly, although human monocyte-derived dendritic cells have both histamine Hj and H2 receptors and can induce CD86 expression by histamine, human epidermal Langerhans cells express neither H nor Hj receptors [72]. 

Schaefer U, Schmitz V. Schneider A. Neugebauer E Histamine induced homologous and heterologous regulation of histamine receptor subtype mRNA expression in cultured endothelial cells. Shock 1999 12 309-315. 

Chand N, Eyre P Classification and biological distribution of histamine receptor subtypes. Agents Actions 1975 5 277-295. 

Fig. 9.8 Examples of rule-of-three compliant molecules that have biological activity better than 10 nM. Under each molecule, the following information is included molecule name, MW, ClogP, the biological activity type, value and target. Target names are as follows D3 and D4 - dopaminergic receptor types 2 and 3 AChE and BChE - acetyl- and butyryl-choline esterases PRa and PRb - progesterone receptor types A and B H] and H3, histamine receptor types 1 and 3 5-HT2a, 5-HT2b, 5-HT2c, 5-HT3, 5-HT4 - serotonin receptor subtypes 2A, 2B, 2C, and types 3 and 4 DAT, NET, 5-HTT - dopamine, norepinephrine and serotonin transporter proteins /X], /x.2, S, ki, ks - opioid receptor types mu-1, mu-2, delta, kappa-1 and kappa-3 5a-Rl and 5o -R2 - 5-alpha-reductase isozymes 1 and 2 Flt-1-fms-like tyrosine kinase receptor.

Histamine (B). Histamine is stored in basophils and tissue mast cells. It plays a role in inflammatory and allergic reactions (p. 72, 326) and produces bronchoconstriction, increased intestinal peristalsis, and dilation and increased permeability of small blood vessels. In the gastric mucosa, it is released from enterochromaffin-like cells and stimulates acid secretion by the parietal cells. In the CNS, it acts as a neuromodulator. Two receptor subtypes (G-pro-tein-coupled), H and H2. are of therapeutic importance both mediate vascular responses. Prejunctional H3 receptors exist in brain and the periphery. 

Seifert R, Hageluken A, Hoer A, Hoer D, Grunbaum L, Offermanns S, Schwaner I, Zinge V, Schunack W, Schultz G (1994) The HI receptor agonist 2-(3-chlorophenyl) histamine activates Gi proteins in HL-60 cells through a mechanism that is independent of known histamine receptor subtypes. Mol Pharmacol... 

In addition to their effects on norepinephrine and serotonin, TCAs have significant antagonistic effects at muscarinic and histaminic receptors. While TCAs appear to bind equally to all subtypes of the muscarinic receptor, they show preferential affinity for the histaminic Hi receptor over the Hi receptor subtype. The... 

Hj, Hj, and Hj receptors are present in the CNS. Tricyclic antidepressant drugs seem to interact with histamine receptors in the CNS. Histamine receptor subtypes in the CNS and the central neurotransmitter role of histamine have been the subject of many recent investigations. Currently there are three central histamine receptors ... 

The biological effects of histamine (Table 15.1) are mediated via three receptor subtypes, HI, H2 and H3 that are linked to G protein but activate different cell-signalling systems. The histamine HI receptor is associated with the phospholipase C-catalysed formation of inositol 1,4,5-triphosphate (IP3) and 1,2-diacylglycerol (DAG). The H2-receptor is coupled to adenylyl cyclase, increasing the production of cAMP. The cellular messenger system involved in H3-receptor activation has not been fully defined, but it may couple to N-type Ca2+-channels. The genes encoding for HI and H2 receptors have been cloned. A mutation of the human H2 receptor has been linked to schizophrenia. 

Small substitutions on the imidazole ring of histamine significantly modify the selectivity of the compounds for the histamine receptor subtypes. Some of these are listed in Table 16-1. 

Occupied receptors for adrenaline, glucagon, ACTH, and histamine activate adenylate cyclase via Gs proteins. Other Gs proteins, which contain subunits designated aolf and which exist as a number of subtypes, mediate olfactory responses. Subunit aD is another specialized polypeptide which is located primarily in neural tissues. A variety of additional G proteins have been discovered in organisms ranging from bacteria to mammals.179 183-186 All have similar structures with 39- to 45-kDa a subunits, 35- to 36-kDa (3 subunits and 5- to 8-kDa y subunits. Whereas the a subunits are unique to each G protein, (3 and y subunits may be shared among several G proteins. These proteins appear to function with many kinds of hormone receptors and... 

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