Histamine Hi- receptor

FIGURE 9.20 Design of multiple ligancl activity, (a) Dual histamine HI receptor and leukotriene receptor antagonist incorporating known antihistaminic properties of cyproheptadine and LTD4. (b) Joint ACE/NEP inhibitor formed from incorporating similarities in substrate structures for both enzymes. From [57],... 

The human histamine Hi-receptor is a 487 amino acid protein that is widely distributed within the body. Histamine potently stimulates smooth muscle contraction via Hi-receptors in blood vessels, airways and in the gastrointestinal tract. In vascular endothelial cells, Hi-receptor activation increases vascular permeability and the synthesis and release of prostacyclin, plateletactivating factor, Von Willebrand factor and nitric oxide thus causing inflammation and the characteristic wheal response observed in the skin. Circulating histamine in the bloodstream (from, e.g. exposure to antigens or allergens) can, via the Hi-receptor, release sufficient nitric oxide from endothelial cells to cause a profound vasodilatation and drop in blood pressure (septic and anaphylactic shock). Activation of... 

Hi-receptors in the adrenal medulla stimulates the release of the two catecholamines noradrenaline and adrenaline as well as enkephalins. In the heart, histamine produces negative inotropic effects via Hr receptor stimulation, but these are normally masked by the positive effects of H2-receptor stimulation on heart rate and force of contraction. Histamine Hi-receptors are widely distributed in human brain and highest densities are found in neocortex, hippocampus, nucleus accumbens, thalamus and posterior hypothalamus where they predominantly excite neuronal activity. Histamine Hrreceptor stimulation can also activate peripheral sensory nerve endings leading to itching and a surrounding vasodilatation ( flare ) due to an axonal reflex and the consequent release of peptide neurotransmitters from collateral nerve endings. 

Fukui, H. (2005). Review of some molecular and physiological studies of histamine HI receptor function (Hiroshi Wada Symposium). Inflamm. Res. 54 (suppl. 1), S52-3. 

Leurs, R., Traiffort, E., Arrang, J. M. et al. (1994). Guinea pig histamine HI receptor. II. Stable expression in Chinese hamster ovary cells reveals the interaction with three major signal transduction pathways. J. Neurochem. 62, 519-27. 

Richelson, E. (1978). Histamine HI receptor-mediated guanosine 3, 5 -monophosphate formation by cultured mouse neuroblastoma cells. Science 201, 69-71. 

Tran, V. T., Chang, R. S. Snyder, S. H. (1978). Histamine HI receptors identified in mammalian brain membranes with [3H]mepyramine. Proc. Natl. Acad. Set USA 75, 6290-4. 

Yamashita, M., Fukui, H., Sugama, K. etal. Expression cloning of a cDNA encoding the bovine histamine Hi receptor. Proc. Natl Acad. Sci. U.S.A. 88 11515-11519,1991. 

Cecchi, M., Passani, M. B., Bacciottini, L., Mannaioni, P. F. and Blandina, P. Cortical acetylcholine release elicited by stimulation of histamine HI receptors in the nucleus basalis magnocellularis a dual-probe microdialysis study in the freely moving rat. Eur. J. Neurosci. 13 68-78, 2001. 

This second-generation histamine HI receptor blocker was put on the world market in the 1980s for the relief of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria [14], Janssen Pharmaceuticals marketed this dmg under the brand name Hismanal. The major benefit of these antihistamines was their... 

Kim, S.F., Huang, A.S., Snowman, A.M., Teuscher, C. and Snyder, S.H. (2007) From the coven Antipsychotic drug-induced weight gain mediated by histamine HI receptor-linked activation of hypothalamic AMP-kinase. Proceedings of the National Academy of Sciences of the United States of America, 104 (9), 3456-3459. 

Cardiovascular effects Harmala alkaloids have cardiovascular effects (Aarons et al. 1977). Harmine, harmaline, and harmalol decrease heart rate, but increase pulse pressure, peak aortic flow, and myocardial contractile force in dogs. Harmine reduces systemic arterial blood pressure and peripheral vascular resistance. Vascular resistance effects are not mediated by jS-adrenergic or histamine HI receptors. 

Histamine Hi receptor Nerve cells, airway and vascular smooth muscles, hepatocytes, chondrocytes, endothelial cells, epithelial cells, neutrophils, eosinophils, monocytes, DC,T and B cells Ca +, cGMP, phospholipase D, phospholipase Aj, NF-kB Gq/n... 

Histamine HI receptor HRHl Agonism Allergic reaction. Antagonism Sedation. 

Histamine Hi receptor antagonists which enter the brain (diphenhydramine, promethazine and others) have sedative actions and polysomnographic recordings have shown that they suppress REM sleep and modestly increase SWS. A rebound in REM sleep sometimes occurs on discontinuation. Stimulation of central Hi and H2 receptors markedly potentiates signals produced by excitatory amino acids and it has been suggested that histamine acts as a waking amine (Schwartz et al., 1986). The effects of centrally acting antihistamines on sleep may be due to inhibition of these effects. 

Miyoshi K, Das AK, Fujimoto K, Horio S, Fukui H. Recent advances in molecular pharmacology of the histamine systems regulation of histamine HI receptor signaling by changing its expression level. J Pharmacol Sci 2006 101 3-6. 

Simons PE, Simons KJ. Clinical pharmacology of new histamine HI receptor antagonists. Clin Pharmacokinet... 

In anesthesia drugs from several groups are used as premedication. Pre-anesthetic medication can decrease the anesthetic doses which otherwise would be required to induce anesthesia and so decrease the risk for adverse effects. Pre-anesthetic medication will increase the rate of induction of anesthesia and can reduce pre-operative pain and anxiety. Drugs include benzodiazepines for sedation and their muscle relaxant properties, opiates for pain relieve and anticholinergics or histamine Hi receptor antagonists against nausea and vomiting. Neuroleptics are also used as premedication for their antiemetic effects. 

M. Higuchi, K. Yanai, N. Okamura, K. Meguro, H. Arai, M. Itoh, R. Iw/ata, T. Ido, T. Watanabe, H. Sasaki, Histamine HI receptors in patients with Alzheimer s disease assessed by positron emission tomography. Neuroscience 99 (2000) 721-729. 

Mechanism of Action A nonsedating antihistamine that exhibits selective peripheral histamine Hi-receptor blocking action. Competes with histamine at receptor sites. Therapeutic Effect Prevents allergic responses mediated by histamine, such as rhinitis and urticaria. 

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... 

The answer is e. (Hardman, p 587. Katzung, p 270.) Chlorpheniramine is a competitive Hi-receptor antagonist that inhibits most responses of smooth muscle to histamine. Hi-receptor antagonists have negligible effects on H2 or EI3 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. 

Common adverse effects of the TCAs, including dry mouth and constipation, are attributable to the potent antimuscarinic effects of many of these drugs. The TCAs also tend to be potent antagonists of the histamine Hi receptor. TCAs such as... 

The vestibular system is important in motion sickness via cranial nerve VIII. It is rich in muscarinic Mi and histamine Hi receptors. 

The flavonoids quercetin, hyperoside and isoquercetin, present in the ethanolic extract of Drosera madagascariensis, are inducers of spasmolytic and anti-inflammatory effects in guinea-pig ileum by affecting cholinergic M3 and histamine HI receptors [183]. 

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