Mast cells, histamine from

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. 

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... 

Inhibitors of histamine release One of the effects of the so-called mast cell stabilizers cromoglycate (cromolyn) and nedocromil is to decrease the release of histamine from mast cells (p. 72, 326). Both agents are applied topically. Release of mast cell mediators can also be inhibited by some Hi antihistamines, e.g., oxatomide and ketotifen, which are used systemically. 

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. 

B) Phenylpiperidine-type opioids releases histamine from mast cells... 

Succinylcholine acts primarily at the skeletal neuromuscular junction and has little effect at autonomic ganglia or at postganglionic cholinergic (muscarinic) junctions. Actions at these sites attributed to succinylcholine may arise from the effects of choline. Succinylcholine has no direct action on the uterus or other smooth muscle structures. It does not enter the CNS and does not cross the placental barrier. It may, however, release histamine from mast cells. Because succinylcholine works by stimulating rather than blocking end plate receptors, anti-AChEs will not reverse muscle paralysis and may actually prolong the block. 

Drugs, particularly organic bases, may release histamine from mast cells by physically displacing the amine from its storage sites. Morphine, codeine, d-tubocu-rarine, guanethidine, and radiocontrast media can release histamine from mast cells. Basic polypeptides, such as bradykinin, neurotensin, substance P, somatostatin, polymyxin B, and the anaphylatoxins resulting from complement activation, also stimulate histamine release. Venoms often contain basic polypeptides as well as the histamine-releasing enzyme phospholipase A. 

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. 

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). 

They were the first presynaptic H3 heteroreceptors to be discovered (in guinea pig mesenteric artery Table 1). They mediate inhibition of transmitter release from many noradrenergic neurons, peripheral as well as central (Table 1). They may be activated by histamine from mast cells, as happens in the heart upon myocardial ischemia (see Section 3.10). In the CNS an input of endogenous histamine has not been demonstrated (see references in Table 3). For example, the release of noradrenaline in the hippocampus of freely moving rats remained unchanged upon local... 

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). 

The term antihistamine, without a modifying adjective, refers to the classic Hi receptor blockers. These compounds do not influence the formation or release of histamine, but rather they competitively block the receptor-mediated response of a target tissue. [Note This contrasts with the action of cromolyn (see p. 220), which inhibits the release of histamine from mast cells and is useful in the treatment of asthma.] The H receptor blockers can be divided into first- and second generation drugs.(Figure 40.5). The first generation drugs are still widely used because they are effective and inexpensive. 

Substance P and the related tachykinins neurokinin A and neurokinin B are mainly found in neurons, particularly unmyelinated sensory somatic and visceral fibres, in enteric sensory neurons and in a number of pathways within the brain. The release of tachykinins from the peripheral ends of these neurons may play an important role in the neurogenic inflammatory responses to local injury and inflammation by promoting the release of histamine from mast cell degranulation, and the release of cytokines from invading white cells, as well as acting directly upon blood vessels to produce vasodilation and plasma extravasation. Neurogenic inflammation within... 

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). 

Studies on the modes of action of dialkylpiperidines have shown that these compounds cause diverse biochemical lesions. These alkaloids which are powerful hemolysins (26) and dermal necrotoxins (27, 28), also release histamine from mast cells ( 9), thus functioning as effective algogens. In addition, these fire ant products inhibit Na+ and K+ ATPases 30) and at low concentrations uncouple oxidative phosphorylation leading to reduced mitochondrial respiration (31). 2,6-Disubstituted... 

Inhibits release of histamine from mast cell Selective Hi antagonist Inhibits type I hypersensitivity... 

Inhibits release of histamine from mast cell Selective Hi antagonist Inhibits type I hypersensitivity Antihistamine Decreases chemotaxis and eosinopil activation Antihistamine Decreases chemotaxis and eosinophil activation Inhibits release of histamine from mast cell Selective Hi antagonist Affinity for H2, ai 2, and 5HT2-receptor... 

Chromolyn sodium, an adjunct in the treatment of asthma, acts to inhibit the release of histamine from mast cells. Cimetidine is a drug that resembles histamine in structure. It competes with histamine for receptors in the stomach, and is useful for reducing gastric acid secretion in the treatment of peptic ulcers. 

Artocarpols from the root barks of Artocarpus rigida have been identified as anti-inflammation agents. Artocarpol C (798) strikingly inhibited the release of y5-glucuronidase and histamine from mast cell degranulation in a concentration-dependent manner (ICso 10.9 and 13.2 //M, respectively). Artocarpol C (798) also showed inhibitory effect on the formyl-peptide-stimulated superoxide anion formation in neutrophils (ICso 26.0 //M) [350]. Artocarpol I (803) exhibited similar inhibition of superoxide anion formation in neutrophils (ICso 10.9 //M) [351]. 

Answer D. The pharmacologic action common to both morphine and D-tubocurarine is the release of histamine from mast cells, causing vasodilation. Morphine increases, but D-tubocurarine (via ganglion blockade) decreases, bladder tone. When used in combination with inhalational anesthetics (e.g., halothane), D-tubocurarine has been implicated in malignant hyperthermia. Morphine relaxes the uterus, but D-tubocurarine has no effects on smooth muscle neurotransmission. 

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