Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peptides released from sensory nerves during an axon reflex are thought to cause mast cell degranulation, histamine (Hi) release and Hi-induced vasodilatation leading to the flare of the triple response. Capsaicin stimulates peptide release from sensory neurones and causes flare in vivo but does not cause Hi release from mast cells in vitro. The effects of capsaicin on mast cell degranulation in human skin in vivo has been studied by histological examination of skin biopsies after topical capsicin (1%) treatment of stratum corneum-denuded forearm in four volunteers. The results show a significant reduction in the visible numbers of mast cells and the appearance of degranulated mast cells ghosts in the skin six hours after capsaicin application. Since capsaicin itself does not release Hi from mast cells, these data suggest that capsaicin-induced release of peptides from neurones could cause mast cell degranulation.
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PMID:The effect of capsaicin application on mast cells in normal human skin. 189 39

1. Systemic capsaicin treatment of the pig depletes the content of sensory neuropeptides (CGRP and tachykinins) in the airways mucosa and skin, without affecting sympathetic and parasympathetic nerves containing NPY and VIP, or the presence and appearance of inflammatory cells including mast cells. Acute capsaicin exposure caused release of sensory neuropeptides and catecholamines, and marked vasodilation in the airways and skin, without signs of plasma protein extravasation or bronchoconstriction. Capsaicin pretreatment effectively desensitizes against local challenges with capsaicin in the airways and skin, as revealed by the absence of vasodilatory responses 2 days later. 2. Cigarette smoke exposure induces marked vasodilatation, lasting for about 5 min in both the upper and lower airways, which seems not to be primarily caused by particulate matter or nicotine in the smoke. Except for a minor capsaicin-sensitive component in the nasal circulation, these responses probably do not involve neural activation, mast cell degranulation or prostaglandin formation. Rather, it is concluded that vapour phase components act on the vessels via unknown mechanisms. 3. Sensitization of pigs with s.c. injections of ascaris antigen was successful, resulting in typical wheal and flare reactions in the skin and bronchoconstriction after local challenge with antigen. The reactivity to ascaris is probably mediated by antibodies of the IgE isotype. 4. Histamine-containing mast cells and sensory neuropeptide-containing nerve fibers show close morphological association around blood vessels in the pig skin. Both alcian blue-positive mast cells and capsaicin-sensitive sensory nerves are present close to the pig airways epithelium. Sensory neuropeptide-containing nerves are also abundant around airways mucosal blood vessels, whereas the bronchial smooth muscle is sparsely innervated. 5. Allergen and histamine injections in the skin caused similar responses consisting of flare and protein extravasation. Allergen challenge in the airways induces marked vasodilatation lasting for 60-90 min in the pig bronchial and nasal circulations. Histamine seems to be important in the early phase (0-20 min) of these responses in the airways, while cyclooxygenase products (possibly PGD2) may be responsible for the longlasting component. A cyclo-oxygenase product is presumably also released from the lung into the circulation after bronchial allergen challenge and thereby induces a delayed, long-lasting nasal vasodilatation. Histamine may be the main bronchoconstrictor agent released in the immediate allergic reaction of the pig. 6. The flare, but not the protein extravasation reaction, to allergen and histamine injections in the skin, was inhibited by capsaicin pretreatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Airways vasodilatation in the immediate allergic reaction. Involvement of inflammatory mediators and sensory nerves. 203 38

Norathyriol, a xanthone aglycon isolated from Tripterospermum lanceolatum, was demonstrated to reduce the plasma leakage elicited by the passive cutaneous anaphylactic reaction in normal as well as in adrenalectomized mice. Capsaicin pretreatment greatly suppressed the local edema caused by antidromic stimulation of the saphenous nerve. The plasma exudation of neurogenic inflammation was also reduced in mice treated with norathyriol, diphenhydramine and methysergide, but not with indomethacin. Norathyriol, cyproheptadine and diphenhydramine combined with methysergide suppressed the ear edema caused by injection of compound 48/80, bradykinin and substance P into the ear. However, indomethacin did not affect this phlogist-induced edema response. Histamine- and serotonin-induced plasma exudation in ear edema was also reduced by norathyriol. In isolated rat peritoneal mast cell preparations, norathyriol produced a dose-dependent inhibition of histamine and beta-glucuronidase release from mast cells challenged by compound 48/80, bradykinin and substance P. In compound 48/80-pretreated mice, norathyriol at higher concentrations suppressed the bradykinin- and substance P-induced ear edema to a significantly greater extent than diphenhydramine combined with methysergide did. These data indicate that the inhibitory effect of norathyriol on local edema is not due to the release of steroid hormones from the adrenal gland, but is probably partly due to suppression of mast cell degranulation and hence reduce the release of chemical mediators which increase vascular permeability, and partly, at least in higher doses, due to protection of the vasculature from challenge by various mediators.
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PMID:Inhibitory effect of norathyriol, a xanthone from Tripterospermum lanceolatum, on cutaneous plasma extravasation. 751 Nov 7

Substance P release by enteric nerves could be an initiating factor for mucosal mast cell (MMC) activation that is associated with weaning in the rat. Capsaicin, which depletes substance P from enteric nerves, should therefore prevent MMC degranulation. Rat pups received either capsaicin (50 mg/kg) or vehicle control subcutaneous injections at 3 and 6 days of life. Capsaicin-treated and control litters were killed at 16, 18, 20, 22, 24 and 26 days of life. MMC activation was measured by serum levels of rat mast cell protease II (RMCPII). Intestinal development was assessed by microdissection to measure villus area, crypt length and crypt cell production rate. RMCPII levels were similar in capsaicin-treated and control rats and peaked at day 22 of life, and intestinal development was not retarded by capsaicin treatment. We conclude that substance P release is unlikely to be an initiating factor for the MMC activation that is associated with weaning.
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PMID:Neuropeptide depletion by capsaicin does not prevent mucosal mast cell activation in the rat at weaning. 808 61

Nerve growth factor (NGF) is known to produce hyperalgesia as well as to stimulate synthesis of neuropeptides in dorsal root ganglia (DRG). In the present study, we wanted to determine the effects of local NGF administration and assess to which extent mast cell-dependent factors are mediating NGF responses. Rats received 1 daily unilateral intraplantar injection for 3 days. Local edema (days 1-3), changes in thermal nociceptive threshold (days 1-4), and the content of calcitonin gene-related peptide (CGRP) and substance P (SP) in the sciatic nerve (day 4), were determined. NGF injection caused edema which was absent in rats pretreated with compound 48/80 as well as in rats treated neonatally with capsaicin ('capsaicin denervation'). NGF-induced edema was not reduced by the neurokinin-1 receptor antagonist SR140333, but attenuated by the CGRP receptor antagonist CGRP[8-37]. On each day, NGF injection caused a decrease in thermal nociceptive threshold which lasted for less than 3 h. Capsaicin denervation, but not treatment with indomethacin, abolished NGF-induced thermal hyperalgesia. Treatment with compound 48/80 attenuated hyperalgesia produced by the first, but not by subsequent, NGF injections. On day 4, 24 h after the last of 3 NGF injections, thermal nociceptive threshold was not different from control values, but at that time, CGRP and SP were elevated in the sciatic nerve. We suggest therefore that NGF-induced local edema was caused by mast cell-derived vasoactive compounds which act together with afferent neuron-derived CGRP to increase vascular permeability. NGF-induced thermal hyperalgesia most likely was caused by an increased sensitivity of peripheral endings of capsaicin sensitive afferents. This effect of NGF was not mediated by products of the cyclooxygenase pathway, and was also observed in mast cell-depleted rats.
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PMID:Intraplantar injection of nerve growth factor into the rat hind paw: local edema and effects on thermal nociceptive threshold. 874 Jun 10

Wasp venoms contain several active components, among them kinin-related peptides. Like bradykinin and [Thr6]bradykinin, Vespula vulgaris venom caused paw oedema following subplantar injection in anaesthetized rats. The oedema was partly inhibited by the bradykinin B2 receptor antagonist icatibant (Hoe 140); the remaining part was abolished by additional pretreatment with 5-hydroxytryptamine (5-HT) receptor antagonists or mast cell depletion. Histamine receptor antagonists were ineffective. Capsaicin pretreatment attenuated oedema formation indicating a neurogenic sensory component. Nociceptive behavioural responses induced by the venom in unanaesthetized rats were abolished by icatibant. It is concluded that kinins, either contained in the venom or released from the tissue, play the predominant role in the inflammatory and algesic effects. The inflammatory effects only partly rely on direct, bradykinin receptor-mediated mechanisms while the remaining part depends on the release of 5-HT from skin mast cells. The algesic effects of the venom are entirely due to direct B2 receptor activation.
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PMID:Vespula vulgaris venom: role of kinins and release of 5-hydroxytryptamine from skin mast cells. 969 10

The mechanisms involved in tachykinin-induced neurokinin-1 (NK(1)) receptor-mediated edema formation have been studied in anesthetized wild-type and NK(1) knockout mice. Intradermally injected substance P (30-300 pmol), NK(1) agonists septide (3-30 pmol) and GR-73632 (3-30 pmol), and the mast cell-degranulating agent, compound 48/80 induced dose-dependent edema in wild-type skin, measured by the accumulation of intravenously injected (125)I-labeled albumin. Septide was 3-10x more potent than substance P. The tachykinins were inactive in knockout mice, but compound 48/80 induced a significantly greater edema (P < 0.05) than that observed in paired wild-type mice. Capsaicin (which releases endogenous neuropeptides) and exogenous tachykinins induced edema formation, which was reduced by the mast cell amine histamine H(1) antagonist mepyramine (P < 0.05). These findings confirm that tachykinins mediate edema formation via the NK(1) receptor and provide direct evidence that the septide-sensitive binding site is on the NK(1) receptor. Furthermore, results suggest that edema induced by the tachykinins, although totally dependent on NK(1) receptor-mediated mechanism, contains a mast cell-dependent component. The evidence is in keeping with an NK(1) receptor on mast cells.
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PMID:Use of NK(1) knockout mice to analyze substance P-induced edema formation. 1044 54

Both the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine and the adenosine A(2B/3) receptor agonist N(6)-benzyl-5'-N-ethylcarboxamido adenosine (N(6)-B-NECA) produce an acute paw oedema response following local s.c. injection into the rat hindpaw. This study characterized aspects of the mechanisms by which these responses occur by determining the effect of compound 48/80 (mast cell depleting agent), capsaicin (sensory neurotoxin) and 6-hydroxydopamine (sympathetic nervous system neurotoxin) on the paw oedema response produced by these agents. Compound 48/80 markedly reduced the increase in paw volume produced by both N(6)-cyclopentyladenosine and N(6)-B-NECA. Capsaicin significantly reduced paw oedema induced by N(6)-cyclopentyladenosine but not N(6)-B-NECA. In contrast, 6-hydroxydopamine reduced paw oedema induced by N(6)-B-NECA but not N(6)-cyclopentyladenosine. These results indicate an involvement of mast cells in paw oedema produced by both adenosine A(1) and A(2B/3) receptor agonists. For N(6)-cyclopentyladenosine, this involvement may be a secondary involvement due to activation of a neurogenic mechanism, but for N(6)-B-NECA, it may be a direct effect on mast cells. The nature of the involvement of the sympathetic nervous system in the action of N(6)-B-NECA is not entirely clear.
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PMID:Involvement of mast cells, sensory afferents and sympathetic mechanisms in paw oedema induced by adenosine A(1) and A(2B/3) receptor agonists. 1078 73

1. This in vitro study was designed to determine the potential use of the NK(1) antagonist, SR140333 as an anti-diarrhoeal treatment for food allergy or inflammatory bowel disease. The effect of various immune and neuronal stimuli on human colonic substance P (SP) release and the effect of SR140333 on subsequently stimulated mucosal ion transport was investigated. 2. Submucosal and sensory nerve fibre stimulation using electrical field stimulation (1 ms/7 Hz/7 V) and capsaicin (50 microM) respectively, mast cell activation by anti-IgE (1/250 dilution) and granulocyte stimulation using fMLP (50 microM) each released SP and evoked a secretory response. 3. SP and the NK(1) selective agonist, Sar-SP (0.1 - 1000 nM) stimulated an increase in colonic secretion which was antagonized by SR140333 (pD'(2)=6.7 and 7.25 versus SP and Sar-SP respectively). 4. SR140333, at a concentration that blocked NK(1)-mediated secretion (500 nM), also reduced the secretory response to both alphaIgE and capsaicin. This suggests a pathophysiologic role for NK(1) receptors. 5. Capsaicin evoked SP release was increased in tissue taken from Crohn's disease but not ulcerative colitis patients. The response to SP was however reduced by 70 and 89% respectively. 6. Mast cells and sensory afferents contribute to allergic diarrhoea. Since SR140333 reduced the secretory response to mast cell and afferent stimulation this compound may be particularly useful in reducing the symptoms of food allergy.
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PMID:Human colonic anti-secretory activity of the potent NK(1) antagonist, SR140333: assessment of potential anti-diarrhoeal activity in food allergy and inflammatory bowel disease. 1149 21

We investigated whether the polycation poly-L-arginine elicited cutaneous vascular hyperpermeability and scratching behavior and, if so, whether these responses involved mast cells and sensory nerves in rats. Intradermal injections of poly-L-arginine induced vascular hyperpermeability and scratching behavior. Combined treatment with chlorpheniramine and methysergide almost completely suppressed the poly-L-arginine (50 microg/site)-induced plasma leakage. Capsaicin desensitization and the tachykinin NK(1) receptor antagonist LY303870, (R)-1-[N-(2-methoxybenzyl)acetylamino]-3-(1H-indol-3-yl)-2-[N-(2-(4-(piperidin-1-yl)piperidin-1-yl)acetyl)amino]propane, partially inhibited the leakage. In mast cell-deficient rats, poly-L-arginine only minimally induced plasma leakage. On the other hand, capsaicin desensitization and LY303870, but not chlorpheniramine or methysergide, suppressed the poly-L-arginine (200 microg/site)-induced scratching. Moreover, poly-L-arginine elicited the scratching even in mast cell-deficient rats. These results suggest that substance P is at least partly involved in both the cutaneous plasma leakage and the scratching behavior induced by poly-L-arginine. Moreover, mast cell-derived amines are suggested to be involved in the plasma extravasation but scarcely, if any, in the scratching behavior.
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PMID:Roles of mast cells and sensory nerves in cutaneous vascular hyperpermeability and scratching behavior induced by poly-L-arginine in rats. 1151 41


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