Histamine receptor subtype

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... 

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. 

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... 

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 ... 

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. 

West RE, Zweig A, Shih NY, Siegel MI, Egan RW, Clark MA (1990) Identification of two H3-histamine receptor subtypes. Mol Pharmacol 38 610-613. 

The third histamine receptor subtype was found to occur on mast cells and to be involved in the synthesis and release of histamine, of nitric oxide and of a series of cytokines, even if the precise immunomodulatory function of H3 receptors is still under investigation. The bulk of data concerning H3 receptors and immunological reactions in different species and different experimental models are summarized in Table 10. 

Ryu, J.H., Yanai, K., Sakurai, E., Kim, C.Y. and Watanabe, T. (1995). Ontogenetic development of histamine receptor subtypes in rat brain demonstrated by quantitative autoradiography. Developmental Brain Res. 87, 101-110. 

Schwartz, J.C., Arrang, J.M., Garbarg, M. and Pollard, H. (1990). A third histamine receptor subtype characterisation, localisation and functions of the H3-receptor. Agents and Actions 30, 13-23. 

Figure 13-2 Histamine receptor subtype location on neuronal and vascular tissues. Activated receptors are associated with neuronal tissue and result mainly in itching. H2 receptors are associated with vascular tissue and result primarily in redness. (Adapted from Abelson MB, Schaefer K. Conjunctivitis of allergic origin immunologic mechanisms and current approaches to therapy. Surv Ophthalmol 1993 38 115-132.)...

Once rcleatted. the physiological effects of histamine arc mediated by specific ccll-surfacc receptors. Extensive pharmacological analysis. suggests the existence of at least three different histamine receptor subtype.s, H. H2. and Hj. 

Pollard H, Bouthenet ML. Autoradiographic visualization of the three histamine receptor subtypes in the brain. In The Histamine Receptor (Schwartz JC, Haas HL, eds). New York Wiley-Liss, 1992 1 79-192. 

Classical leukocyte chemoattractant effects that occur are blocked by thioperamide, an H3/H4 antihistamine. Other H3 receptor ligands, such as R-a-methylhlstamlne and Imetit, also are agonists at H4 receptors, but they have lower affinity than at H3 receptors (Table 37.12). Clobenpropit Is a partial agonist at H4 receptors, but It Is an H3 antihistamine (inverse agonist). Thioperamide is an inverse agonist at H4 and H3 receptors. 4-Methylhistamine (Fig. 37.22) has greater affinity (>100-fold) for H4 receptors than other histamine receptor subtypes (66). 

A model of histamine synthesis and mobilization in the gastric mucosa, as described by G. Kahlson in 1964. He postulated a feedback control of the histamine-forming capacity (HFC) of the mucosa by the histamine content of the mucosa itself. Some 30 years later, the validity of this prescient suggestion appears substantiated by the identification of different histamine receptor subtypes on the enterochro-maffin-like cell and their ability to regulate histamine secretion. 

Compound 2 showed an IC50 value of 0.72 nM at hHs, a 150-fold improvement over 1. 2 displayed excellent selectivity over other histamine receptor subtypes and 60 CNS receptors. 2 and its analogues appeared to be ideal H3 PET tracer candidates based on their overall profile. Evaluation of 2-based tracers in the MRL imaging research group is ongoing. The synthesis, SAR, and profiles of this novel class of H3 inverse agonists will be presented. 

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