Histamine type 2 receptor

Griswold DE, Alessi S, Badger AM, Poste G, Hanna N. Differential sensitivity of T suppressor cell expression to inhibition by histamine type 2 receptor antagonists. J Immunol 1986 137 1811-1815. 

Ligands of the histamine Hs-receptors, new potent antagonists of the 2-thioimi-dazole type 97F295. 

Endou M, Poli E> Levi R Histamine H3 receptor signaling in the heart possible involvement of Gj/Go proteins and N-type Ca channels. J Pharmacol Exp Ther 1994 269 221. bS... 

Because the vestibular system is replete with muscarinic-type cholinergic and histaminic (Hx) receptors, anticholinergics and antihistamines are the most commonly used pharmacologic agents to prevent and treat motion sickness. 

Nakamura, H., Sano, H., Yamazaki, M., Sugiyama Y., Carrier-mediated active transport of histamine H2 receptor antagonists, cimetidine and nizatidine, into isolated rat hepato-cytes contribution of type I system,... 

The histamine H4-receptor which was discovered in 2001 has been shown to have a role in chemo-taxis and mediator release in various types of immune cells including mast cells, eosinophils, dendritic cells and T cells. H4-receptor antagonists have been shown to have anti-inflammatory properties and efficacy in a number of disease models, such as those for asthma and colitis in vivo. Cinnarizine has a high affinity for the H4-receptor. Recently other H4-receptor antagonists have been developed with high receptor affinity and specificity. The first few studies into the function of H4-receptors suggested... 

Three types of histamine (H) receptors have been isolated. At present, it appears that receptor blockade... 

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. 

In conclusion, histamine H3 receptors have multiple locations in the gastric mucosa, occurring in different cell types, according to the different animal species however, the final effect on acid secretion seems to be an inhibitory one, although in a particular experimental model of the mouse, a stimulatory effect seems to be predominant. A scheme representing the multiple locations of H3 receptors in the gastric mucosa from available data is reported in Figure 2. 

As far as the inhibitory mechanism of H3-receptors is concerned, the effect of (R)a-methylhistamine is decreased by pretreatment with pertussis toxin and, like the 012-adrenoceptor- and Aj-adenosine receptor-mediated effects, it is potentiated by oo-conotoxin GVIA, a blocker of the N-type Ca channel (Endou et al., 1994). One may conclude from these findings that presynaptic histamine H3-receptors are probably coupled to a pertussis toxin-sensitive Gi/Go protein, which exerts a negative control on the neuronal Ca++-currents, that are responsible for the exocytotic release of noradrenaline. 

Histamine H3 receptors are well distributed in peripheral tissues, although relatively less abundant than in the CNS. As for the cellular localization, peripheral H3 receptors are present in different cell types, like the neural, paracrine, endocrine, muscular and endothelial cells, where they subserve a predominant inhibitory role. However, the multiple location of H3 receptors in the same tissue may lead to opposite effects on the physiologic function, thus, their role can sometimes be quite difficult to understand. As regards a possible clinical application of H3 ligands, although many suggestions have been derived from the experimental animal data (e.g. gastric disorders, asthma, myocardial ischemia, hypertension and inflammation), to date, no clinical evidence is available for any therapeutic indication. 

Endou, M., Poli, E., Levi, R., 1994. Histamine H3-receptor signaling in the heart Possible involvement of Gi/Go proteins and N-type Ca++ channels. J. Pharmacol. Exp. Ther. 269, 221-229. 

Thus, FUB 307 (42) may be regarded as a kind of retard prodrug and represents the first reported compound of the azomethine prodrug type and particularly the first histamine H3 receptor agonist to possess such prolonged in vivo pharmacokinetics [45],... 

Koyama M, Heerdt PM, Levi R (2003) Increased severity of reperfusion arrhythmias in mouse hearts lacking histamine H3-receptors. Biochem Biophys Res Commun 306 792-6 Koyama S, Brodie MS, Appel SB (2007) Ethanol inhibition of M-current and ethanol-induced direct excitation of ventral tegmental area dopamine neurons. J Neurophysiol 97 1977-85 Kuzhikandathil EV, Yu W, Oxford GS (1998) Human dopamine D3 and D2l receptors couple to inward rectifier potassium channels in mammalian cell lines. Mol Cell Neurosci 12 390 102 Kuzhikandathil EV, Oxford GS (1999) Activation of human D3 dopamine receptor inhibits P/Q-type calcium channels and secretory activity in AtT-20 cells. J Neurosci 19 1698-1707... 

Histamine receptors are related to skin barrier function.44 Three different types of histamine receptors, HI, H2, and H3 have been reported. First, topical application of histamine HI and H2 receptor antagonists accelerated the barrier repair. Histamine itself, H2 receptor agonist, and histamine releaser delayed the barrier repair. Histamine H3 receptor antagonist and agonist did not affect the barrier recovery rate. Topical application of the HI and H2 receptor antagonists prevented the epidermal hyperplasia induced by barrier disruption under low humidity. The mechanism of the relationship between the histamine receptors and the barrier repair process has not been elucidated yet. 

The affinities (Tab. 13.1) and rank order of affinities (Tab. 13.2) of clozapine-type compounds clearly show that their primary receptor targets are serotonin (excep. 5-HTj), histamine Hj and adrenergic receptors, followed by dopamine receptors. Whilst clozapine and olanzapine seem to have some similarities in their overall receptor profile, quetiapine differs from them not only in the significantly lower absolute affinity values but also in the rank order of potencies that is, it has the highest affinity for adrenergic alpha-1 and histamine H, receptors followed by 5-HT2A and dopamine receptors. 

Adamantidis MM, Lacroix DL, Caron JF, Dupuis BA (1995) Electrophysiological and arrhythmogenic effects of the histamine type 1-receptor antagonist astemizole on rabbit Purkinje fibers Clinical relevance. J Cardiovasc Pharmacol 26 319-327... 

Parietal cells possess receptors for three stimulators of acid secretion neural (acetylcholine, muscarinic-type receptor), paracrine (gastrin) and endocrine control (histamine, H2 type receptor) (Figure 4.2). 

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