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)

Vasoactive intestinal peptide (VIP) has potent protective activity against sepsis and increases the survival rate of septic rats and mice. The present study was planned to evaluate the effect of VIP on mast cell activity, histamine and methylhistamine levels and oxidative stress in the liver and kidneys of septic rats. The effect of VIP was compared to that of nitric oxide synthesis inhibition, previously tested extensively in septic shock models, with doubtful benefit. The present study showed that endotoxic shock did not lead to oxidative stress in either liver or kidney of the rats. On the other hand, mast cells, based on their location, displayed functional heterogeneity to the septic insults. VIP possibly modulated the specific reactions of the tissues to mediators released from mast cells during septic shock. The most prominent effect of VIP as compared to nitric oxide synthesis inhibition was related to mast cells. In conclusion, the prevention of mast cell reactivity by VIP could be a potential therapeutic strategy in controlling septic shock.
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PMID:Vasoactive intestinal peptide inhibits degranulation and changes granular content of mast cells: a potential therapeutic strategy in controlling septic shock. 1070 23

Mastocytosis encompasses a range of disorders characterized by overproliferation and accumulation of tissue mast cells. Mast cell disease is most commonly seen in the skin, but the skeleton, gastrointestinal tract, bone marrow, and central nervous system may also be involved. We present a 10-year-old boy with diffuse cutaneous mastocytosis characterized by disseminated papular, nodular, and infiltrated leathery lesions. The patient presented with chronic diarrhea and malnutrition. Laboratory studies were normal except for an elevated urinary 1-methylhistamine level. The bone marrow aspirate showed a dense mast cell infiltrate confirming systemic involvement.
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PMID:Diffuse cutaneous mastocytosis with bone marrow infiltration in a child: a case report. 1088 51

Histamine is an inflammatory mediator present in mast cells, which are abundant in the wall of the gallbladder. We examined the electrical properties of gallbladder smooth muscle and nerve associated with histamine-induced changes in gallbladder tone. Recordings were made from gallbladder smooth muscle and neurons, and responses to histamine and receptor subtype-specific compounds were tested. Histamine application to intact smooth muscle produced a concentration-dependent membrane depolarization and increased excitability. In the presence of the H(2) antagonist ranitidine, the response to histamine was potentiated. Activation of H(2) receptors caused membrane hyperpolarization and elimination of spontaneous action potentials. The H(2) response was attenuated by the ATP-sensitive K(+) (K(ATP)) channel blocker glibenclamide in intact and isolated smooth muscle. Histamine had no effect on the resting membrane potential or excitability of gallbladder neurons. Furthermore, neither histamine nor the H(3) agonist R-alpha-methylhistamine altered the amplitude of the fast excitatory postsynaptic potential in gallbladder ganglia. The mast cell degranulator compound 48/80 caused a smooth muscle depolarization that was inhibited by the H(1) antagonist mepyramine, indicating that histamine released from mast cells can activate gallbladder smooth muscle. In conclusion, histamine released from mast cells can act on gallbladder smooth muscle, but not in ganglia. The depolarization and associated contraction of gallbladder smooth muscle represent the net effect of activation of both H(1) (excitatory) and H(2) (inhibitory) receptors, with the H(2) receptor-mediated response involving the activation of K(ATP) channels.
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PMID:Actions of histamine on muscle and ganglia of the guinea pig gallbladder. 1096 Mar 63

Histamine release from mast cells is a primary mediator of rhinorrhea, nasal mucosal swelling, increased secretion, sneezing, pruritus and congestion that occur in allergic rhinitis. It is well known that histamine H(1) receptor antagonists inhibit the itch and rhinorhea, but do not block the allergic nasal congestion. A growing body of evidence shows that in addition to histamine H(1) receptors, activation of H(3) receptors may contribute to the procongestant nasal actions of histamine. Activation of the prejunctional histamine H(3) receptor modulates sympathetic control of nasal vascular tone and resistance. The present study was conducted to further characterize the role of histamine H(3) receptors on neurogenic sympathetic vascular contractile responses in isolated porcine nasal turbinate mucosa. We presently found that the histamine H(3) receptor agonist, (R)-alpha-methylhistamine (10-1000 nM), inhibited electrical field stimulation-induced sympathetic vasomotor contractions in a concentration-dependent fashion. Pretreatment with either of the selective histamine H(3) receptor antagonists, thioperamide and clobenpropit, blocked the sympathoinhibitory effect of (R)-alpha-methylhistamine in porcine turbinate mucosa. The effect of compound 48/80, an agent that elicits the release of endogenous histamine from mast cells on nasal sympathetic contractile responses, was also tested. The action of compound 48/80 to release mast cell-derived histamine in the nose mimics many of the nasal responses associated with allergic rhinitis, extravascular leakage and decreased nasal patency. We presently found that compound 48/80 also inhibited the electrical field stimulation-induced sympathetic response. Pretreatment with the H(3) receptor antagonist clobenpropit blocked the sympathoinhibitory action of compound 48/80 on sympathetic contractile responses in nasal mucosa. Taken together, these studies indicate that histamine H(3) receptors modulate vascular contractile responses by inhibition of noradrenaline release from sympathetic nerve terminals in nasal mucosa. It is further suggested that histamine H(3) receptors may play a role in the regulation of vascular tone and nasal patency in allergic nasal congestive disease.
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PMID:Histamine H3 receptor activation inhibits neurogenic sympathetic vasoconstriction in porcine nasal mucosa. 1235 75

Thirty-seven patients with mastocytosis and unexplained elevated levels of urinary N-methylhistamine who were undergoing bone marrow biopsy were studied with respect to the diagnosis of mastocytosis and the manifestations of the disease. These patients were from a group of 66 patients from whom a bone marrow biopsy was obtained and urinary N-methylhistamine levels were measured in the period 1990-1998. In seven (19%) of the 37 patients, mastocytosis was limited to the skin. Five (14%) of the 37 patients showed accumulation of mast cells in the bone marrow without characteristic skin lesions, whereas seven (19%) of the 37 patients showed increased numbers of mast cells both in the skin and the bone marrow. Eighteen (49%) of the 37 patients with elevated N-methylhistamine did not have mast cell accumulation in either the skin or the bone marrow biopsy. The median level of N-methylhistamine in the urine of patients with mastocytosis limited to the skin was 245 micro mol/mol creatinine. The average level of N-methylhistamine was 509 micro mol/mol creatinine in patients with mast cell accumulation in the bone marrow and cutaneous mastocytosis. There was a significant difference in the levels of N-methylhistamine in patients with mast cell accumulation in the bone marrow biopsy compared with those without. The likelihood of mastocytosis with mast cell accumulation in the bone marrow biopsy at a given level of N-methylhistamine was calculated. It was established that an N-methylhistamine level of 297 micro mol/mol creatinine or higher may be considered as a threshold indicator for obtaining a bone marrow biopsy in patients suspected of mastocytosis with mast cell accumulation in the bone marrow. For practical purposes, we propose to consider the cut-off level of approximately 300 micro mol/mol N-methylhistamine creatinine for this assay.
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PMID:Urinary N-methylhistamine as an indicator of bone marrow involvement in mastocytosis. 1237 95

Osteoporosis is increasingly being recognized in men. Secondary causes are often implicated, but the mechanism of bone loss remains unclear in about a third of patients. The mast cell is a complex cell that stores a number of factors known to affect bone metabolism. Patients with systemic mastocytosis often demonstrate osteoporosis and bone marrow mast cells may be increased in osteoporotic postmenopausal women. We address the possible role of the mast cell in the pathophysiology of male osteoporosis by studying the relationship between bone marrow infiltration with mast cells and the 24 h urine excretion of N-methylhistamine, and the severity of osteoporosis in 48 consecutive men with idiopathic osteoporosis (bone mineral density Z score of <-1 and/or at least one prevalent vertebral fracture). Secondary causes for osteoporosis were excluded and none of the patients had systemic manifestations of enhanced mast cell activity. A widely variable number of morphologically normal mast cells were counted in toluidine blue-stained sections from 42 of 46 evaluable bone marrow biopsies. In 4 of the 42 biopsies (9%), clusters of abnormal mast cells were identified. These four patients were the only ones who also demonstrated increased 24 h urine excretion of N-methylhistamine. There was a significant positive relationship between mast cell number and the 24 h urine excretion of N-methylhistamine reflecting mast cell activity (p = 0.0001), and this latter measurement correlated negatively with bone mineral density (BMD) at the lumbar spine (p < 0.001). We identified clinically important bone marrow cell infiltration with pathologic mast cells in the absence of systemic manifestations of mast cell hyperactivity as an additional secondary cause for osteoporosis in some 9% of men with idiopathic osteoporosis, and found urinary excretion of N-methylhistamine to be above the upper limit of the normal laboratory reference range diagnostic for this cause of secondary osteoporosis. The more continuous spectrum in the relationship between mast cell activity and BMD supports a potential role for this cell in the pathogenesis of idiopathic male osteoporosis.
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PMID:A potential role for the mast cell in the pathogenesis of idiopathic osteoporosis in men. 1247 68

The aim of this study was to investigate if mannitol inhalation, as a model of exercise-induced bronchoconstriction (EIB), causes mast cell activation and release of mediators of bronchoconstriction. Urinary excretion of previously identified mediators of EIB was investigated in association with mannitol-induced bronchoconstriction. Twelve asthmatic and nine nonasthmatic subjects inhaled mannitol and urine was collected 60 min before and for 90 min after challenge. The urinary concentrations of leukotriene (LT)E4, the prostaglandin (PG)D2 metabolite and the mast cell marker 9alpha,11beta-PGF2 were measured by enzyme immunoassay. N(tau)-methylhistamine was measured by radioimmunoassay. In asthmatic subjects, inhalation of a mean+/-SEM dose of 272+/-56 mg mannitol induced a reduction in forced expiratory volume in one second (FEV1) of 34.5+/-2.1%. This was associated with increases in urinary 9alpha,11beta-PGF2 (91.9+/-8.2 versus 66.9+/-6.6 ng x mmol creatinine(-1), peak versus baseline) and LTE4 (51.3+/-7.5 versus 32.9+/-4.7). In nonasthmatic subjects, the reduction in FEV1 was 1.0+/-0.5% after inhaling 635 mg of mannitol. Although smaller than in the asthmatics, significant increases of urinary 9alpha,11beta-PGF2 (68.4+/-6.9 versus 56.0+/-5.8 ng x mmol creatinine(-1)) and LTE4 (58.5+/-5.3 versus 43.0+/-3.3 ng x mmol creatinine(-1)) were observed in the nonasthmatic subjects. There was also a small increase in urinary excretion of N(tau)-methylhistamine in the nonasthmatics, but not in the asthmatics. The increased urinary levels of 9alpha,11beta-prostaglandin F2 support mast cell activation with release of mediators following inhalation of mannitol. Increased bronchial responsiveness to the released mediators could explain the exclusive bronchoconstriction in asthmatic subjects.
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PMID:Evidence of mast cell activation and leukotriene release after mannitol inhalation. 1451 40

Daily treatment of systemic mastocytosis with high-dose interferon-alfa often is not tolerated because of clinical or hematologic side effects. We report successful treatment of a patient with systemic mastocytosis, who was positive for the D816V mutation, with interferon alfa-2b at 10 million units three times per week. During 5 years of treatment, bone marrow infiltration by mast cells decreased from 50 to < or =5%, and there was a decrease (urinary N-methylhistamine excretion, 75%; serum tryptase concentration, 98%) or normalization (serum calcitonin value, urinary prostaglandin F2alpha excretion) of mast cell mediators. Side effects included mild depression (untreated) and biochemical hypothyroidism easily managed with supplemental levothyroxine.
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PMID:Successful treatment of systemic mastocytosis with high-dose interferon-alfa: long-term follow-up of a case. 1560 59

Migraine may affect as many as 9% of all schoolchildren and often presents with abdominal symptoms of pain, nausea, and vomiting. Even though the pathophysiology of migraine remains unknown, self-regulation techniques appear to be more effective in prevention of childhood migraine than conventional pharmacotherapy which is often associated with adverse effects. Mast cells have been implicated in the pathogenesis of migraine in adults, but have not been previously studied in children with migraine. Mast cells are found close to the vessels and nerves in the meninges where they can release multiple vasoactive, neurosensitizing, and pro-inflammatory mediators. Therefore, we investigated whether children with migraine may have increased urinary levels of mast cell mediators and whether practicing relaxation imagery exercises has an effect on the frequency of headache, as well as on mast cell activation. Urine was collected for 24 hours from children with and without migraine after a 5-day amine-restricted diet. Children with migraine also collected urine during migraine episodes. The mean levels of urinary histamine, its main metabolite, methylhistamine, and the mast cell enzyme, tryptase, were higher in children than generally found in adults, but they did not differ statistically in any of the categories studied. However, in 8 of 10 children who practiced relaxation imagery techniques and successfully reduced the number of migraines, the urine tryptase levels were also significantly lower. There was no relationship between successful practice and sex or age of the child. These results suggest that stress may activate mast cells which could be involved in the pathophysiology of migraine.
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PMID:Mast cell activation in children with migraine before and after training in self-regulation. 1561 2

Postural tachycardia syndrome (POTS) is a disabling condition that commonly affects otherwise normal young females. Because these patients can present with a flushing disorder, we hypothesized that mast cell activation (MCA) can contribute to its pathogenesis. Here we describe POTS patients with MCA (MCA+POTS), diagnosed by episodes of flushing and abnormal increases in urine methylhistamine, and compared them to POTS patients with episodic flushing but normal urine methylhistamine and to normal healthy age-matched female controls. MCA+POTS patients were characterized by episodes of flushing, shortness of breath, headache, lightheadedness, excessive diuresis, and gastrointestinal symptoms such as diarrhea, nausea, and vomiting. Triggering events include long-term standing, exercise, premenstrual cycle, meals, and sexual intercourse. In addition, patients were disabled by orthostatic intolerance and a characteristic hyperadrenergic response to posture, with orthostatic tachycardia (from 79+/-4 to 114+/-6 bpm), increased systolic blood pressure on standing (from 117+/-5 to 126+/-7 mm Hg versus no change in POTS controls), increased systolic blood pressure at the end of phase II of the Valsalva maneuver (157+/-12 versus 117+/-9 in normal controls and 119+/-7 mm Hg in POTS; P=0.048), and an exaggerated phase IV blood pressure overshoot (50+/-10 versus 17+/-3 mm Hg in normal controls; P<0.05). In conclusion, MCA should be considered in patients with POTS presenting with flushing. These patients often present with a typical hyperadrenergic response, but beta-blockers should be used with great caution, if at all, and treatment directed against mast cell mediators may be required.
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PMID:Hyperadrenergic postural tachycardia syndrome in mast cell activation disorders. 1571 Jul 81


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