Histamine receptors distributions

Hill SI (1990) Distribution, properties and functional characteristics of three classes of histamine receptor. Pharmacol Rev 42 45-83... 

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

Mechanism of Action A propylamine derivative antihistamine that competes with histamine for histamine receptor sites on cells in the blood vessels, gastrointestinal (GI) tract, and respiratory tract. TAerapfiMtic Effect Inhibits symptoms associated with seasonal allergic rhinitis such as increased mucus production and sneezing. Pharmacokinetics Well absorbed after PO and parenteral administration. Food delays absorption. Widely distributed. Metabolized in liver. Primarily excreted in urine. Not removed by dialysis. Half-life 20 hr. 

Although histamine is distributed in the gallbladder, its functional effects have been identified only following activation of Hi and H2 receptors which mediate muscle contraction and relaxation, respectively (Impicciatore 1978) The H3 receptor agonist (R)a-... 

Korte, A., Myers, J., Shih, N.Y., Egan, R.W., Clark, M.A., 1990. Characterization and tissue distribution of H3 histamine receptors in guinea pigs by N -methylhistamine. Biochemical. Biophysical. Res. Comm. 168, 979-986. 

Ganellin, C. R. Characterization and distribution of histamine receptors. In The chemical regulation of biological mechanisms Creighton, A. M. Turner, S. Eds. Royal Society of Chemistry London, U.K., 1982 pp. 1-15. 

HiU SJ. Distribution and functional characteristics of the three classes of histamine receptors. Pharmacol Rev 1990 42 45-83. 

Histamine receptors were reviewed in 1973 before the advent of the H2 antagonists later developments are described in reference 4, and the subject was mentioned briefly in these reports in 1975 and 1977. The classification and distribution of histamine receptors has been discussed by Black and reviewed by Chand and Eyre. The Physiological Society of Philadelphia held a symposium on histamine receptors in 1977, the proceedings of which are in press. A symposium was held in 1978 at the Vlth International Conference on Medicinal Chemistry, Brighton, England (proceedings to be published). In addition, there have been several symposia on H2-receptor histamine antagonists, mainly concerned with clinical aspects. 

A comprehensive review of histamine receptors in the cardiovascular system has Ijeen published. Histamine lowers blood pressure by causing widespread vasodilatation in most animal species but the effects are complex to analyse. It is clear that both H and H2 receptors are involved, but their distribution and effect varies depending on the species and particular vascular bed under study. Both types of antagonist have to be administered together to fully block many of the vascular effects of... 

F. Antohe, C. Heltianu, and N. Simionescu. Further evidence for the distribution and nature of histamine receptors on microvascular endothelium. Microcirc. Endoth. Lymph. 3 163-185 (1986). 

Rotter A, Frostholm A (1986) Cerebellar histamine-Hl receptor distribution An autoradiographic study of Purkinje cell degeneration, staggerer, weaver and reeler mutant mouse strains. Brain Res. Bull, 16,205-214. 

Histamine receptors have been classified into two major subtypes, H, and H2, on the basis of quantitative studies on isolated peripheral tissues. Histamine H,-receptors mediate the contractile actions of histamine on numerous visceral smooth muscles, most notably from the trachea, ileum and uterus of the guinea-pig [36-39]. These responses are antagonized by the classical -antihistamines [36-39] such as mepyramine (1) [36] and diphenhydramine (3) [40] (see Figure 2.1). Histamine also stimulates the secretion of acid by stomach, increases the rate of contraction of guinea-pig isolated atria and inhibits electrically evoked contractions of rat isolated uterine horn [41 ]. However, these responses are not affected by H, -receptor antagonists and have been defined as histamine H2-receptor responses following the development of specific antagonists to these responses such as burimamide [41], cimetidine [42] and ranitidine [43]. The distribution and classification of histamine H,-and H2-receptors in various mammalian peripheral tissues have been reviewed elsewhere [44-46a]. 

Vasodilation Vasodilation, the most important vascular effect of histamine, involves both Hj and Hj receptors distributed throughout the resistance vessels in most vascular beds. Activation of either the Hj or Hj receptor can elicit maximal vasodilation, but the responses differ. Hj receptors have a higher affinity for histamine and mediate an endothelium-NO-dependent dilation that is relatively rapid in onset and short-lived. By contrast, activation of Hj receptors (stimulating the cyclic AMP-PKA pathway in smooth muscle) causes dilation that develops more slowly and is more sustained. 

Histamine immunoreactive neurons have been identified in the tuberal region of the posterior hypothalamus (tuberomammilary nucleus), projecting to nearly all parts of the brain. Three histamine receptors are known histamine-related functions in the central nervous system (CNS) are regulated at postsynaptic sites by the H and H2 receptors, while the H3 receptor exhibits the features of a presynaptic autoreceptor, mediating the synthesis and release of histamine. The Hi receptor is widely distributed in the CNS. It is present in all areas and layers of the cerebral cortex, limbic system, caudate putamen, nucleus accumbens, thalamus, hypothalamus, mesencephalon, and lower brainstem and spinal cord. The H2 and H3 receptors are also distributed extensively and in a heterogeneous fashion in the CNS. Regarding the role of histamine in the CNS, there is substantial evidence that it plays a role in control of the sleep/wake cycle. Whether the... 

It became of interest to study the chemical properties of these compounds to gain some insights into how they may interact with the H2 histamine receptor. The analysis was simplified by concentrating on a series of antagonists depicted in Fig. 1 whose structures were closely related to cimetidine. The stodies emphasized the importance of such physicochemical properties as geometry, acidity (pX ), hydrophilicity (octanol-water partition, P) and dipole moment (electron density distribution). 

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. 

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