Histamine in mast cells

The stores of histamine in mast cells can be released through several mechanisms. 

No Heparin Heparin normally occurs as a macromolecule complexed with histamine in mast cells where its physiologic role is unknown. It is extracted for commercial use from porcine intestine or bovine lung. Heparin is a mixture of straight-chain anionic glycosaminoglycans... 

Uvnas, B. (1967). Mode of binding and release of histamine in mast cell granules of the rat. Fed. Proc. 26, 919-221. 

The histamine release in the brain, and perhaps other sites, involves exocytosis, as this potassium-induced release is a calcium-dependent process. Histamine is released by many factors. For example, histamine is released by numer-ons drugs including reserpine, codeine, meperidine, hydralazine, morphine, d-tnbocurarine, dextrans, papaverine, and compound 48/80. However, the different histamine storage sites show certain degrees of specificity. For example, the histamine in mast cells is not released following potassium-induced depolarization or by reserpine, factors that release histamine from nenrons. Conversely, compound 48/80, which releases histamine from mast cells, is not able to release histamine from nenrons. 

For the presence of histamine in mast cells, see Riley JF, West GB. The presence of histamine in tissue mast cells. J Physiol Land 120 528-537, 1953. For the presence of mast cells in hog gastric mucosa see idem. Mast cell histamine in hog stomach. J Physiol Lond 130 3P, 1955. 

Histamine in the Cardiovascular System. It has been known for many years that histamine is present in sympathetic nerves and has a distribution within the heart that parallels that of norepinephrine (see Epinephrine and norepinephrine). A physiological role for cardiac histamine as a modulator of sympathetic responses is highly plausible (15). A pool of histamine in rat heart located neither in mast cells nor in sympathetic nerves has been demonstrated. The turnover of this metaboHcaHy active pool of histamine appears to be maintained by normal sympathetic activity. 

Mast cells express high-affinity IgE Fc receptors (FceRI) on their surface, contain cytoplasmic granules which are major sources of histamine and other inflammatory mediators, and are activated to release and generate these mediators by IgE-dependent and non-IgE-dependent mechanisms [1]. Disturbances either in the release of mast cell mediators or in mast cell proliferation are associated with clonal mast cell disorders including monoclonal mast cell activation syndrome (MMAS) and mastocytosis respectively, which are in turn associated with some cases of anaphylaxis [2], Molecular mechanisms have been identified which may link increased releasability of mast cell mediators and conditions leading to increased mast cell numbers [3]. Patients with mastocytosis have an increased risk to develop anaphylaxis [4, 5] and those with anaphylaxis may suffer from unrecognized mastocytosis or may display incomplete features of the disease [6-8]. 

There are a number of side-effects of opiates that are due to their actions on opiate receptors outside the central nervous system. Opiates constrict the pupils by acting on the oculomotor nucleus and cause constipation by activating a maintained contraction of the smooth muscle of the gut which reduces motility. This diminished propulsion coupled with opiates reducing secretion in the gut underlie the anti-diarrhoeal effect. Opiates contract sphincters throughout the gastrointestinal tract. Although these effects are predominantly peripheral in origin there are central contributions as well. Morphine can also release histamine from mast cells and this can produce irritation and broncho-spasm in extreme cases. Opiates have minimal cardiovascular effects at therapeutic doses. 

Histamine, formed by the decarboxylation of histidine, is stored in mast cells and basophils some other tissues can synthesize histamine but... 

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... 

Somatostatin (SOM), initially identified by its ability to inhibit the release of growth hormone, is known to have inhibitory effects on a variety of cells [ 109], In mast cells and in basophils, SOM, like NT, has inhibitory as well as stimulatory effects depending on the concentration used. At high concentrations (> 10 8 M), SOM is a powerful stimulus of peritoneal mast-cell secretion (from both normal and athymic rats) and resembles other non-immunologic secretagogues such as compound 48/80, SP and NT in that it triggers a rapid exocytosis that is primarily dependent on cellular Ca [ 110,111], A similar effect is seen in vivo when injected into skin or skin blisters at high concentrations (> 10-8 M), SOM causes a rapid, dose-dependent release of histamine [88, 112] but when used at concentrations lower than those which elicit a secretory... 

The classical cellular sources of histamine are mast cells and basophils, gastric enterochromaffin-like cells, platelets and histaminergic neurons. Interestingly the cells in the immune system, which do not store histamine, show high HDC activity and are capable of production of high amounts of histamine, which is secreted immediately after synthesis [20]. These cells include platelets, monocytes/macrophages, DCs, neutrophils, and T and B lymphocytes. 

In mast cells, histamine release induced by IgE or A23187 was also inhibited by feverfew extract [48] which also reduced spasmolytic activity of smooth muscle induced by acetylcholine, 5HT, histamine, prostaglandin E2 and bradykinin [20]. 

The lung is relatively rich in histamine-containing mast cells, so it is not surprising that a number of investigators have assessed the role of histamine in the pulmonary toxicity observed after ozone exposure. 

Unwanted effects produced by d-tu-bocurarine result from a nonimmune-mediated release of histamine from mast cells, leading to bronchospasm, urticaria, and hypotension. More commonly, a fall in blood pressure can be attributed to ganglionic blockade by d-tu-bocurarine. 

Mast Cells and Basophils. The chief sites of histamine storage are mast cells in the tissues and basophils in blood. These cells synthesize histamine and store it in secretory granules along with a heparin-protein complex. In response to specific antigens, mast cells or basophils are sensitized. Histamine is then secreted from the storage granules. Besides the histamine stores in mast cells and basophils, there is evidence of non-mast cell histamine in some tissues, particularly gastric and intestinal mucosa (60). 

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. 

Histamine is released from mast cells in antigen-antibody reactions, as in anaphylaxis and allergy, which are the most widely known physiological reactions to histamine. However, these potentially fatal reactions are not caused by histamine alone. Other agents present in mast cells, such as serotonin, acetylcholine, bradykinin (a nonapeptide), and a slow-reacting substance or leukotriene (see chapter 8) also contribute. In the stomach, where histamine induces acid secretion, its release seems to be regulated by the peptide hormone pentagastrin. 

Histamine is found in most of the tissues, present in various biological fluids. In most tissues, histamine exists in bound form in granules, in mast cells or basophils. These mast cells are especially rich at sites of potential tissue injury i.e. skin, lungs, liver, GIT etc. and is unevenly distributed. It is also present in many venoms (of bees wasps), bacteria and plant tissues. 

Most tissue histamine is sequestered and bound in granules (vesicles) in mast cells or basophils the histamine content of many tissues is directly related to their mast cell content. The bound form of histamine is biologically inactive, but as noted below, many stimuli can trigger the release of mast cell histamine, allowing the free amine to exert its actions on surrounding tissues. Mast cells are especially rich at sites... 

Action NSAID Dose 1 gtt qicl Caution [C, +] Disp Opthal soln SE Local irritation EMS None OD Unlikely to cause life-threatening Sxs Ketotifen (Zaditor) [Ophthalmic Anrihistamine/Histamine Antagonist Mast Cell Stabilizer] Uses Allergic conjunctivitis Action Hrreceptor antagonist, mast cell stabilizer Dose Adults Peds. 1 gtt in eye(s) q8—12h Caution [C, /—] Disp Soln SE Local irritation, HA, rhinitis EMS None OD Unlikely to cause life-threatening Sxs... 

Receptors for histamine, which probably acts as a neuromodulator,801 occur in the brain.802 Histamine is formed by decarboxylation of histidine (p. 745)803 and is inactivated by histidine N-methyltransferase. Histamine is best known for its presence in mast cells,804 components of the immune system that release histamine during inflammatory and allergic reactions (Chapter 31). However, histaminergic neurons of the hypothalamus extend throughout the whole forebrain,805 and specific receptors have been found both in the brain and in peripheral tissues.806 Several other amines that are formed by decarboxylation of amino acids are present in trace amounts but may have im-... 

Results obtained in mucin-secreting goblet cells, which will be reviewed here, and in histamine-secreting mast cells, which have been presented elsewhere [2], are prompting us to abandon some long-established ideas about packing and release in secretion and to sketch a new hypothesis based on current polymer-gel theory. 

Much like what was described in heart and lung, neuropeptides may release histamine from mast cells, which in turn may act on presynaptic H3-receptors (Matsubara et al., 1992). In this regard, endogenous histamine exerts a two faceted influence on neurogenic inflammation, since this substance may also cause vasodilatation and rise in vascular permeability through the Hi-receptor/NO-pathway (Levi et al., 1991 Lassen et al., 1995). 

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