Histamine physiological mediator

Both exocytotic and nonexocytotic mechanisms can contribute to adverse drug reactions that involve histamine release. Histamine is only one of several potent physiological mediators that are released from mast cells the other substances can also contribute to the overall immediate hypersensitivity reaction. 

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. 

The physiological and pharmacological effects of histamine are mediated through four different receptors Hi, Hj, Hj, and Ht, all members of the 7-transmembrane g protein-coupled receptor (GPCR) family with amino terminal glycosylation sites and phosphorylation sites for protein kinases A and C. The receptors are widely expressed on different tissues that are responsive to histamine. For the Hi receptor these tissues include smooth muscle cells of the airways and vasculature, the gastrointestinal tract, cardiovascular system, neutrophils, endothelial cells, T and B cells, hepatocy tes, nerve... 

The physiological and pharmacological effects of histamine are mediated throngh four different receptors Hi, H2, H3, and Ht, all members of the 7-ttansmembrane g protein-conpled receptor (GPCR) family with amino terminal glycosylation sites and phosphorylation sites for protein kinases A and C. 

Histamine is a biogenic amine that is widely distributed in the body and functions as a major mediator of inflammation and allergic reactions, as a physiological regulator of gastric acid secretion in the stomach, as a neurotransmitter in the central nervous system (CNS) and may also have a role in tissue growth and repair. 

Histamine is a mediator of several physiological and pathological processes within and outside the nervous system 249 The chemical structure of histamine has similarities to the structure of other biogenic amines, but important differences also exist 250... 

Knowledge of the physiological role of histamine in the CNS and evidence for the existence of discrete neuronal networks that could be called histaminergic are still evolving. Histamine-mediated hypothermia, emesis, and hypertension have been shown to exist, and the well-known sedative effects of Hj antihistamines are centrally mediated. 

Histamine was synthesized in 1907 and later isolated from mammalian tissues. Early hypotheses concerning the possible physiologic roles of tissue histamine were based on similarities between the effects of intravenously administered histamine and the symptoms of anaphylactic shock and tissue injury. Marked species variation is observed, but in humans histamine is an important mediator of immediate allergic (such as urticaria) and inflammatory reactions, although it plays only a modest role in anaphylaxis. Histamine plays an important role in gastric acid secretion (see Chapter 62) and functions as a neurotransmitter and neuromodulator (see Chapters 6 and 21). Newer evidence indicates that histamine also plays a role in chemotaxis of white blood cells. 

Direct cardiac effects of histamine include both increased contractility and increased pacemaker rate. These effects are mediated chiefly by H2 receptors. In human atrial muscle, histamine can also decrease contractility this effect is mediated by H receptors. The physiologic significance of these cardiac actions is not clear. Some of the cardiovascular signs and symptoms of anaphylaxis are due to released histamine, although several other mediators are involved and appear to be more important than histamine in humans. 

The effects of histamine released in the body can be reduced in several ways. Physiologic antagonists, especially epinephrine, have smooth muscle actions opposite to those of histamine, but they act at different receptors. This is important clinically because injection of epinephrine can be lifesaving in systemic anaphylaxis and in other conditions in which massive release of histamine—and other mediators— occurs. 

In conclusion, available data indicate that H3 receptors can mediate inhibitory effects on intestinal motility. However, it is still unclear whether these effects have a physiologic significance. On the one hand, the lack of involvement of histamine H3 receptors in the control... 

Histamine is not only a mediator of several (patho)physiological actions, but also functions as a neurotransmitter, both centrally as peripherally [1, 2]. Feedback mechanisms are crucial to neurotransmission and the presynaptic histamine H3 receptor not only plays a key role in regulating histamine release but also regulates the release of other neurotransmitters (for further details see chapter 2 and 3). Because inhibitory effects on histamine H3 receptor-mediated stimuli by G protein toxins (both cholera and pertussin toxin) have been reported, it is most likely that the histamine H3 receptor also belongs to the superfamily of G protein-coupled receptors [3,4], i.e. coupled to a G protein of the Gi/0 class [5]. The reader is referred to chapter 6 for more details. 

Histamine A chemical produced by various cells in the body that is involved in the modulation of certain physiologic responses (e.g., secretion of gastric acid), as well as in the mediation of hypersensitivity (allergic) responses. 

Histamine was synthesized in 1907 and later isolated from mammalian tissues. Early hypotheses concerning the possible physiologic roles of tissue histamine were based on similarities between histamine s actions and the symptoms of anaphylactic shock and tissue injury. Marked species variation is observed, but in humans histamine is an important mediator of immediate allergic and... 

Apart from its role as a major mediator of inflammation and allergic reactions and as physiological regulator of gastric acid secretion, histamine is also a neurotransmitter in the CNS. Central histaminergic cell bodies are located in the posterior hypothalamus and project diffusely to almost all brain regions and to the spinal cord. There are four types of histamine receptors, all G-protein-coupled, Hi, H2, H3 and H4. Hi receptors couple to Gq/11 proteins. H2 receptors couple to Gs. H3 and H4 receptors couple to Gi/o. 

Of their many preformed intracellular mediators, histamine, not only plays an important physiological role, but can be used as a marker for these cells. In the human peripheral blood, the basophil is the only leukocyte that contains histamine. As a result, histamine release from human blood leukocyte preparations can be used to monitor basophil degranulation. In this chapter we will describe the histamine release assay, alternative techniques to measure the concentration of histamine and, finally, a method to purify human basophils to confirm that the chemokines are acting directly on the basophil. 

This is most effectively achieved by physiological antagonism of bronchial muscle contraction, namely by stimulation of adrenergic bronchodilator mechanisms. Pharmacological antagonism of specific bronchoconstrictors is less effective either because individual mediators are not on their own responsible for a large part of the bronchoconstriction (acetylcholine, adenosine, leukotrienes) or because the mediator is not even secreted during asthma attacks (histamine). 

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