Histamine causing release

When exposure is repeated, the allergen binds between two adjacent IgE molecules. This causes release of inflammatory mediators (histamine, leukotrienes, chemotactic factors). These act locally and cause smooth muscle contraction, increased vascular permeability, mucous gland secretion, and infiltration of inflammatory cells (neutrophils and eosinophils). However, histamine can also be released by non-IgE-mediated mechanisms (e.g., due to exposure to certain fungi). 463... 

The surrounding redness caused by the vasodilatation of local blood vessels in the skin (hyperaemia). Histamine released at the site of contact acts on sensory nerve endings in the skin. Impluses travel along the axon to other peripheral branches of the same neuron to cause release of vasodilataory peptide neurotransmitters from nerve endings serving a wider area of skin than the initial contact point. Impluses reaching the CNS are interpreted as itch and pain. 

The naturally occurring substance histamine causes blood capillaries to dilate and smooth muscle to contract. Most cells release it in response to wounding, allergies, and most inflammatory conditions. Antihistamines block the production of this substance, thereby combating a painful swelling. 

Inhaled and intravenous histamine causes bronchoconstriction as one of the first recognized properties of histamine, which is inhibited by Hi antihistamines. As a manifestation of airway hyperresponsiveness, asthmatic individuals are more sensitive to the bronchoconstrictor effect of histamine than normal individuals. In addition, in vitro studies have shown increased histamine release in basophils and mast cells obtained from asthmatic subjects compared with... 

An important example of PLP-dependent amino acid decarboxylation is the conversion of histidine into histamine. Histamine is often involved in human allergic responses, e.g. to insect bites or pollens. Stress stimulates the action of the enzyme histidine decarboxylase and histamine is released from mast cells. Topical antihistamine creams are valuable for pain relief, and oral antihistamines are widely prescribed for nasal allergies such as hay fever. Major effects of histamine include dilation of blood vessels, inflammation and swelling of tissues, and narrowing of airways. In serious cases, life-threatening anaphylactic shock may occur, caused by a dramatic fall in blood pressure. 

A slow intravenous injection of histamine produces marked vasodilation of the arterioles, capillaries, and venules. This causes a fall in blood pressure whose magnitude depends on the concentration of histamine injected, the degree of baroreceptor reflex compensation, and the extent of histamine-induced release of adrenal catecholamines. Vasodilation of cutaneous blood vessels reddens the skin of the face, while a throbbing headache can result from vasodilation of brain arterioles. Vasodilation is mediated through both Hj- and Hj-receptors on vascular smooth muscle. Stimulation of Hj-receptors produces a rapid and short-lived response, whereas stimulation of H2-receptors produces a more sustained response that is slower in onset. Stimulation of Hj-receptors on sympathetic nerve terminals inhibits the release of norepinephrine and its associated vasoconstriction. 

Dilation of arterioles results in an irregular red flare over an area that is generally wider than that due to the capillary dilation. The flare probably results from an axon reflex in which histamine stimulates autonomic nerve endings, causing release of vasodilatory mediators. 

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. 

Nerve endings 5-HT is less potent than histamine in releasing catecholamines from adrenal medulla. S-HT receptors located on various sensory neurons mediate a depolarising response, which may cause pain itching. 

Endogenous histamine has a modulating role in a variety of inflammatory and immune responses. Upon injury to a tissue, released histamine causes local vasodilation and leakage of plasma-containing mediators of acute inflammation (complement, C-reactive protein) and antibodies. Histamine has an active chemotactic attraction for inflammatory cells (neutrophils, eosinophils, basophils, monocytes, and lymphocytes). Histamine inhibits the release of lysosome contents and several T- and B-lymphocyte functions. Most of these actions are mediated by H2 or H4 receptors. Release of peptides from nerves in response to inflammation is also probably modulated by histamine, in this case acting through presynaptic H3 receptors. 

In humans, injection or infusion of histamine causes a decrease in systolic and diastolic blood pressure and an increase in heart rate. The blood pressure changes are caused by the direct vasodilator action of histamine on arterioles and precapillary sphincters the increase in heart rate involves both stimulatory actions of histamine on the heart and a reflex tachycardia. Flushing, a sense of warmth, and headache may also occur during histamine administration, consistent with the vasodilation. Vasodilation elicited by small doses of histamine is caused by H -receptor activation and is mediated primarily by release of nitric oxide from the endothelium (see Chapter 19). The decrease in blood pressure is usually accompanied by a reflex tachycardia. Higher doses of histamine activate the H2-mediated cAMP process of vasodilation and direct cardiac stimulation. In humans, the cardiovascular effects of small doses of histamine can usually be antagonized by Hi-receptor antagonists alone. 

In response to the attachment of the antigen to the IgE antibodies, the macrophages release mediators such as histamine, which causes release of further mediators such as cytokines and leukotrienes. These inflammatory mediators cause the dilation and increased permeability of blood vessels and constriction of smooth muscles. 

Morphine by releasing Histamine causes Orthistatic Hypotension... 

Urticaria, commonly known as hives, is a type I allergic reaction that results very rapidly from exposure to a toxicant to which the subject has become sensitized. It is characterized by the release of histamine from a type of white blood cell. Histamine causes many of the symptoms of allergic reaction, including tissue edema. In addition to edema, erythema, and accompanying raised welts on skin, urticaria is accompanied by severe itching. In severe cases, such as happen in some people as the result of bee or wasp stings, urticaria can result in systemic anaphylaxis, a potentially fatal allergic reaction. 

Release of histamine The release of histamine may be the primary response to some stimuli, but most often, histamine is just one of several chemical mediators released. Stimuli causing the release of histamine from tissues include the destruction of cells as a result of cold, bacterial toxins, bee sting venoms, or trauma. Allergies and anaphylaxis can also trigger release of histamine. 

Histamine receptors variously mediate the bronchoconstrictant, inflammatory, irritant, vasodilator, gastric pepsin secretion and immune suppression actions of histamine. Associated with the immune response, cytokines cause release of histamine from mast cells. Histamine acts via HI, H2, H3 and H4 GPCRs. HI and H2 receptors couple via both Gas (elevating cAMP) and Gaq (elevating Ca2+ in a pertussis toxin-insensitive fashion) and H3 couples via Gai (decreasing cAMP). 

Urticaria due to intake of tartrazine is more widely accepted as an adverse effect and has been demonstrated in a number of studies. During this reaction substances such as histamine are released into the blood which cause the symptoms of red weals on the skin and itching. A number of other food colours and other types of food additives can also cause urticaria and there may be cross-reactivity between colours such as eryth-rosine and sunset yellow. A challenge of patients whose urticaria had improved on a colour-free diet with 0.15 mg of tartrazine, resulted in three out of thirteen developing urticaria within three hours of exposure."... 

As noted, mast cells and their mediators are integral components of the allergic response. Histamine, the main mediator involved in type I allergic reactions, is released from mast cells and basophils. Histamine is synthesized and stored in nearly all tissues, with especially high concentrations in the lungs, skin, stomach, duodenum, and nasal mucosa. Histamine causes smooth muscle contraction, increased vascular permeability, vasodilation,... 

Histamine acts as a local hormone (autacoid) similarly to serotonin or prostaglandins, i.e. it acts within the immediate vicinity of its site of release. In the context of gastric secretion, for example, stimulation of receptors on the histamine-containing cell causes release of histamine which in turn acts on receptors on parietal cells which then secrete hydrogen ions (see Gastric secretion, Ch. 31). 

Histamine is released in many allergic states, but it is not the sole cause of S5unptoms, other chemical mediators, e.g., leukotrienes and prostaglandins, also being involved. Hence the usefulness of Hj-receptor antihistamines in allergic states is variable, depending on the extent to which histamine, rather than other mediators, is the cause of the clinical manifestations. 

Tubocurarine can cause release of histamine by direct mast cell degranulation which can result in systemic effects, such as cutaneous flushing, local wheal and flare formation, hypotension, and occasionally bronch-ospasm. Preoperative oral terfenadine 60 mg + ranitidine 150 mg attenuated the reduction in blood pressure but not cutaneous flushing after the administration of tubocurarine and morphine in 60 women undergoing elective gynaecological surgery in a placebo-controlled study (122). 

Significant physiological functions not occurring in mast cells have been found for heparin and histamine (3,4,5,6). In this form the agents are synthesized and released as required. Thus, in the intestine, in response to a meal of fat, secretion of histamine causes increased vessel permeability and fat transport, while secretion of heparin causes release of DAO to destroy the histamine in a negative feedback cycle (see Figure 8). 

Histamine was discovered in 1910 and is released from cells when they are injured. An injured cell also stimulates production of histamine by the action of histadine carboxylase. The freed histamine causes capillaries to dilate and smooth muscles to contract. This results in a reddening of the area, itching or pain by a reaction with nerve endings, and a local edema from increased cell wall permeability. 

Histamine, produced in many tissues, is s)mthesized by removing the carboxyl group from the amino acid histidine (Figure 16.8). It has many, often anno)dng, physiological roles. Histamine is released during the allergic response. It causes the itchy skin rash associated with poison ivy or insect bites. It also promotes the red, watery eyes and respiratory s)tmptoms of hay fever. 

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