Histamine from mast cells, mechanism

Dietary copper deficiency increases the acute inflammatory response in rats and other small laboratory animals (Schuschke et al. 1994). The release of inflammatory mediators, such as histamine and serotonin, from mast cells increases the vascular permeability of postcapillary venules and results in edema. In copper-deficient rats, release of histamine from mast cells correlates positively with frequency of the acute inflammatory response. Copper-deficient rats (0.6 mg Cu/kg DW ration for 4 weeks) have more mast cells in muscle than copper-adequate controls given diets containing 6.3 mg Cu/kg DW ration however, histamine content of mast cells is not affected (Schuschke et al. 1994). An early clinical sign of copper deficiency is a reduction in the number of circulating neutrophils the mechanism for copper-deficient neutropenia (leukopenia in which... 

Mechanism of Action A mouth agent that has anti-allergic and anti-inflammatory properties. Appears to inhibit formation and/or release of inflammatory mediators (e g., histamine) from mast cells, neutrophils, mononuclear cells. Therapeutic Effect Alleviates signs and symptoms of aphthous ulcers. 

In myocardial ischemia, several of the mechanisms presented above come into play. First, neuropeptides such as CGRP are released from cardiac sensory C fibers and subsequently release histamine from mast cells as just mentioned. Histamine then can act at least at two presynaptic H3 heteroreceptors on the C fibers to attenuate further neuropeptide release (Section 3.9), and on postganglionic sympathetic fibers to attenuate exocytotic as well as carrier-mediated noradrenaline release (Section 3.3). Both presynaptic effects are potentially beneficial. The H3 receptors are unique in this pattern of effects. Presynaptic adenosine Ai receptors, when activated, also inhibit both exocytotic and carrier-mediated noradrenaline release, but cardiac Ai receptors in addition mediate negative chronotropic and dro-motropic effects. Presynaptic 0C2-adrenoceptors, when activated, reduce exocytotic noradrenaline release but enhance carrier-mediated noradrenaline release (due to stimulation of the Na+/H+ exchanger, Imamura et al. 1996b), which is the major mode of noradrenaline release and the major arrhythmogenic risk in protracted myocardial ischemia (see Levi and Smith 2000 Koyama et al. 2003). 

About the same time Amann and Werle showed the complex of heparin with histamine and other di- and polyamines, and they also suggested a displacement mechanism in the release of histamine from mast cells. Schayer ... 

Antibody-independent activation of the complement system starting with C3 can be achieved by means of CVF (cobra venom factor), which interacts with a serum cofactor. The CVF-serum cofactor complex acts on C3 and activates the terminal complement sequence (Fig. 8). The result may be cytolysis if bacteria or erythrocytes are involved, or the activation of a noncytolic mechanism such as the release of histamine from mast cells, platelets, or leukocytes, enhanced phagocytosis, contraction of smooth muscles, the aggregation and fusion of platelets, or the promotion of blood coagulation. 

Mechanisms of Complement Activation. Complement is a major mediator of the inflammatory response. Complement recruits and enlists the participation of humoral and cellular effector systems, induces histamine release from mast cells and directs migration of leukocytes (chemotaxis), in addition to producing phagocytosis and the release of lysosomal constituents from phagocytes. 

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. 

Histamine may be released from mast cells by mechanisms that do not require prior sensitization of the immune system. Drugs, high-molecular-weight proteins, venoms, and other substances that damage or disrupt cell membranes can induce the release of histamine. Any thermal or mechanical stress of sufficient intensity also will result in histamine release. Cytotoxic compounds, may release histamine as the result of disruption of cell membranes. 

Mechanism of Action A mast cell stabilizer that prevents the activation and release of inflammatory mediators, such as histamine, leukotrienes, mast cells, eosinophils, andmonocytes.T herapeuticEffect Prevents both early and late asthmatic responses. Pharmacokinetics The extent of absorption is 7% to 9% of a single inhaled dose of 3.5 to 4 mg and 17% of multiple inhaled doses, with absorption largely from the respiratory tract. Although most of the inhaled dose is subsequently swallowed, only 2% to 3% is absorbed from the G1 tract. Less than 4% of the total dose is systemically absorbed following multiple doses of ophthalmic solution. Protein binding 89%. Not metabolized. Excreted in urine. Half-life 1.5-3.3 hr. 

Most anaphylactoid reactions are due to a direct or chemical release of histamine, and other mediators, from mast cells and basophils. Immune-mediated hypersensitivity reactions have been classified as types I-IV. Type I, involving IgE or IgG antibodies, is the main mechanism involved in most anaphylactic or immediate hypersensitivity reactions to anaesthetic drugs. Type II, also known as antibody-dependent hypersensitivity or cytotoxic reactions are, for example, responsible for ABO-incompatible blood transfusion reactions. Type III, immune complex reactions, include classic serum sickness. Type IV, cellular responses mediated by sensitised lymphocytes, may account for as much as 80% of allergic reactions to local anaesthetic. 

No information was located regarding the mechanism by which tetryl enters the blood stream from the lungs, skin, or gastrointestinal tract, the mechanism by which tetryl is transported in the blood stream, or the mechanism of toxicity for tetryl. Earlier studies suggested that the cause of tetryl-induced dermatitis, which is the most common and widely studied adverse effect, may be both physical (direct irritation by sharp tetryl crystals) and chemical (by reacting with components of the skin) (Ruxton 1917). The chemical hypothesis was later advanced by others as well (Bain and Thompson 1954 Brownlie and Cumming 1946). Bain and Thompson (1954) specifically suggested that histamine release may result from a tetryl-induced sensitization reaction or from direct tetryl-induced release from mast cells. 

The mechanism by which cyclooxygenase inhibition produces bronchospasm in susceptible individuals is unknown. Arachidonic acid metabolism through the 5-lipoxygenase pathway may lead to the excess production of leukotrienes C4 and D4. Leukotrienes C4, D4, and E4 produce bronchospasm and promote histamine release from mast cells, whereas the administration of leukotriene receptor antagonists and 5-lipoxygenase inhibitors ablate the pulmonary and nonpuhnonary responses to aspirin in aspirin-sensitive asthmatics. The precise mechanism by which augmented leukotriene production occurs is unknown, and available hypotheses do not explain why only a small number of asthmatic patients react to aspirin and NSAIDs. 

Alm PE, Bloom GD. 198 lb. What - if any - is the role of adrenergic mechanisms in histamine release from mast cells Agents Actions ll( /2) 60-66. 

Epinephrine and isoproterenol (via cAMP mechanisms) and theophylline (via cAMP or block of adenosine receptors) inhibit the release of mediators from mast cells and basophils and cause bronchodilation. Diphenhydramine competitively blocks histamine actions at H, receptors, actions that would otherwise cause bronchoconstriction and increased capillary permeability. Dexamethasone has multiple cellular effects, including inhibition of IgE-producing clone proliferation, block of T helper cell function, and anti-inflammatory actions. Most of the actions of glucocorticoids result from decreases in the synthesis of cytokines (eg, interleukins, platelet activating factor) or eicosanoids (leukotrienes, prostaglandins). 

Bradykinin is a potent vasodilator that causes contraction of nonvascular smooth muscle, increases vascular permeability and it is also involved in the mechanism of pain. It has similar actions to histamine, and, like histamine, it is released from venules rather than arterioles. Bradykinin stimulates nitric oxide (NO) production by vascular endothelium. Histamine, released from mast cells in response to injury, inflammation or allergic responses, causes arteriolar vasodilatation, venous constriction in some vascular beds, and increased capillary permeability. 

The Mechanism of Histamine Release from Mast Cells with Reference to the Action of Antiallergic Drugs... 

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