Mast cell receptors, tissue

Immunoglobulins can also be receptors. For example, molecules of IgE bound to basophils and the related mast cells of tissues serve as receptors for allergens. Binding of an allergen to the IgE molecules stimulates the release of granules containing histamine and other substances (Chapter 31). 

Adenosine is produced by many tissues, mainly as a byproduct of ATP breakdown. It is released from neurons, glia and other cells, possibly through the operation of the membrane transport system. Its rate of production varies with the functional state of the tissue and it may play a role as an autocrine or paracrine mediator (e.g. controlling blood flow). The uptake of adenosine is blocked by dipyridamole, which has vasodilatory effects. The effects of adenosine are mediated by a group of G protein-coupled receptors (the Gi/o-coupled Ai- and A3 receptors, and the Gs-coupled A2a-/A2B receptors). Ai receptors can mediate vasoconstriction, block of cardiac atrioventricular conduction and reduction of force of contraction, bronchoconstriction, and inhibition of neurotransmitter release. A2 receptors mediate vasodilatation and are involved in the stimulation of nociceptive afferent neurons. A3 receptors mediate the release of mediators from mast cells. Methylxanthines (e.g. caffeine) function as antagonists of Ai and A2 receptors. Adenosine itself is used to terminate supraventricular tachycardia by intravenous bolus injection. 

Bradykinin is also released from mast cells within damaged tissues. It produces inflammation and activates nociceptors via bradykinin B1 and B2 receptors. 

Fig. 2. IgG-mediated systemic versus local anaphylaxis, a IgG-mediated systemic anaphylaxis. When allergen-IgG immune complexes are formed in the circulation, basophils immediately capture them through IgG receptors on their surface and are activated to release PAF, that in turn act on vascular endothelial cells, leading to increased vascular permeability, b Passive cutaneous anaphylaxis. When allergen-IgG immune complexes are formed in the skin, they stimulate tissue-resident mast cells to release chemical mediators such as histamine, leading to local inflammation. 

The allergen-specific IgE antibody binds to the high affinity Fc receptor for IgE on the surface of tissue mast cells and circulating basophils. IgE can also be found in... 

Neurotensin (NT) is a tridecapeptide (Table 4.2) first isolated from brain and gut by Carraway and Leeman [75] and reported by them to induce a rapid and transient hypotension, a cutaneous vasodilatation, and a cyanosis of the extremities in the anaesthetized rat. This report, along with others [76-78] indicating that the NT-induced hypotension and increased vascular permeability could be blocked by histamine receptor antagonists such as mepy-ramine [77] or by pretreatment with compound 48/80 [76], suggested that endogenous histamine (perhaps released from tissue mast cells) was involved in producing some of the biological effects of NT [78]. 

Histamine H4 receptor High expression on bone marrow and peripheral hematopoietic cells, eosinophils, neutrophils, DC,T cells, basophils, mast cells Low expression in nerve cells, hepatocytes peripheral tissues, spleen, thymus, lung, small intestine, colon and heart Enhanced Ca +, inhibition of cAMP ... 

Histamine (B). Histamine is stored in basophils and tissue mast cells. It plays a role in inflammatory and allergic reactions (p. 72, 326) and produces bronchoconstriction, increased intestinal peristalsis, and dilation and increased permeability of small blood vessels. In the gastric mucosa, it is released from enterochromaffin-like cells and stimulates acid secretion by the parietal cells. In the CNS, it acts as a neuromodulator. Two receptor subtypes (G-pro-tein-coupled), H and H2. are of therapeutic importance both mediate vascular responses. Prejunctional H3 receptors exist in brain and the periphery. 

Histamine, an important mediator (local signaling substance) and neurotransmitter, is mainly stored in tissue mast cells and basophilic granulocytes in the blood. It is involved in inflammatory and allergic reactions. Histamine liberators such as tissue hormones, type E immunoglobulins (see p. 300), and drugs can release it. Histamine acts via various types of receptor. Binding to Hi receptors promotes contraction of smooth muscle in the bronchia, and dilates the capillary vessels and increases their permeability. Via H2 receptors, histamine slows down the heart rate and promotes the formation of HCl in the gastric mucosa. In the brain, histamine acts as a neurotransmitter. 

Classically, these receptors have also been divided into three groups. The first of these, the Hj receptors, were described by Schild in 1966. The Hj receptors were discovered in 1972 by Black et al. The Hj receptor subtype was described by Arrang in 1983. The Hj receptor is found in the smooth muscle of the intestines, bronchi, and blood vessels and is blocked by the classical antihistamines. The Hj receptor, present in gastric parietal cells, in guinea pig atria, and in the uterus, does not react to H, blockers but only to specific Hj antagonists. Hj receptors also appear to be involved in the immunoregulatory system and may be present in T lymphocytes, basophil cells, and mast cells. Hj receptors are found predominantly in brain but are also localized in stomach, lung, and cardiac tissue. 

By a negative feedback control mechanism mediated by H2 receptors, histamine appears to modulate its own release and that of other mediators from sensitized mast cells in some tissues. In humans, mast cells in skin and basophils show this negative feedback mechanism lung mast cells do not. Thus, histamine may act to limit the intensity of the allergic reaction in the skin and blood. 

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-... 

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