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

Neurogenic inflammation has been proposed as a possible pathogenetic mechanism for migraine and cluster headache. Antidromic stimulation of trigeminal fibers causes plasma protein extravasation, mast cell activation and degranulation, vacuolation and increase in endothelial vesicle number within post capillary venules in rat dura mater. The antimigraine drugs sumatriptan and dihydroergotamine block the development of plasma extravasation and ultrastructural changes, as well as plasma calcitonin gene-related peptide (CGRP) increase in the superior sagittal sinus following electrical trigeminal ganglion stimulation. Sumatriptan and dihydroergotamine bind with high affinity to the 5-HT1D/1B receptors, thus suggesting that their neurogenic antiinflammatory activity is mediated by activation of 5-HT autoreceptors present on sensory fibers innervating blood vessels in dura mater.
 ...
PMID:The trigemino-vascular system and migraine. 137 7

Neurogenic plasma extravasation, endothelial cell activation (increase in vesicle number and vacuole formation), platelet aggregation and adhesion, and mast cell degranulation occur selectively in post-capillary venules of the dura mater following electrical trigeminal ganglion stimulation, and are mediated by release of neuropeptides from perivascular unmyelinated C fibres. Pre-treatment with the antimigraine drugs dihydroergotamine and sumatriptan, two drugs that bind with high affinity to 5-HT1B/1D receptors, markedly attenuated plasma protein extravasation induced by electrical trigeminal ganglion stimulation. Trigeminal stimulation increased plasma calcitonin gene-related peptide levels in rat superior sagittal sinus. Pre-treatment with dihydroergotamine and, to a lesser extent, sumatriptan, attenuated this increase. Both drugs reduced morphological changes in post-capillary venules and mast cells within dura mater following electrical trigeminal ganglion stimulation. Plasma protein extravasation was selectively blocked in dura mater (but not in extracranial tissues) by pre-treatment with those receptor agonists showing a rank order of potency suggesting a 3-HT1B/1D interaction (5-CT greater than 5-BT greater than DHE greater than sumatriptan greater than 8-OH-DPAT). Pre-treatment with 5-HT2 and 5-HT3 antagonists was not effective. Taken together, these data are consistent with the interpretation that putative 5-HT-1B/1D receptors located on sensory fibres are coupled to inhibition of peptide release and blockade of neurogenic inflammation. An important therapeutic action of ergot alkaloids and sumatriptan in migraine headaches is so defined.
 ...
PMID:Evidence for 5-HT1B/1D receptors mediating the antimigraine effect of sumatriptan and dihydroergotamine. 166 Mar 51

Review of the atopic diseases suggests a redefinition of the term "atopy" is indicated to reflect new information that has become available during the 60 years since the term was introduced. Atopy may be viewed as a manifestation of a still undefined defect. It is characterized by certain clinical findings and frequently by derangement of the immune and autonomic nervous systems. The atopic diseases are a group of seemingly unrelated conditions--eczema, asthma, rhinitis, hypertrophic sinusitis, and perhaps vernal conjunctivitis and migraine--which cluster in individuals and families. In the respiratory tract and eye, eosinophils in the tissues and secretions are characteristic and are not dependent on the presence of immediate hypersensitivity. Symptoms suggestive of basophil and mast cell mediator release are common to all the atopic diseases, and there is some evidence that nonimmunologic mediator release is enhanced in atopic patients. In the most clearly defined atopic diseases, eczema and asthma, approximately 80% of patients have an increased IgE response to normal environmental allergens. Accompanying and perhaps underlying these enhanced IgE responses are deficiencies of T cell numbers and function particularly in the suppressor T lymphocytes. Evidence exists that decreased beta-2-adrenergic and increased cholinergic and alpha-adrenergic responsiveness accompany and perhaps underlies the atopic diseases irrespective of the presence or absence of allergy.
 ...
PMID:The Bela Schick lecture for 1985. The atopic diseases. 286 4

Stress is known to precipitate or worsen a number of disorders, such as migraines, in which mast cells are suspected of being involved by releasing vasoactive, nociceptive, and proinflammatory mediators. However, no functional association has been demonstrated yet between a migraine trigger and brain mast cell activation. Nontraumatic immobilization (restrain) stress has been shown to stimulate the hypothalamic-pituitary-adrenal axis and to cause redistribution of immune cells. Here, restrain stress caused degranulation in 70% of rat dura mast cells within 30 min, as shown both by light and electron microscopy. These morphologic findings were accompanied by cerebrospinal fluid elevation of rat mast cell protease I, but not II, indicating secretion from connective tissue type mast cells. Mast cell activation due to stress was abolished in animals that had been treated neonatally with capsaicin, indicating that neuropeptides in sensory nerve endings are involved in this response. Complete inhibition was also achieved by pretreating the animals ip with polyclonal antiserum to CRH. Mast cells in the dura were localized close to nerve processes containing substance P, but no CRH-positive fibers were identified even though these were found close to mast cells in the median eminence. This is the first time that stress is shown to activate intracranial mast cells; apparently through the sequential action of CRH and sensory neuropeptides. These findings may have implications for the pathophysiology and possible therapy of neuroinflammatory disorders such as migraines, which are induced or exacerbated by stress.
 ...
PMID:Stress-induced intracranial mast cell degranulation: a corticotropin-releasing hormone-mediated effect. 758 32

Interstitial cystitis, a sterile bladder condition, is characterized by urinary frequency, urgency, burning and suprapubic pain. Increasing evidence indicates that interstitial cystitis is a heterogeneous syndrome that reflects an immune response to a variety of triggers. More than 50% of the patients have allergies, 30% have the irritable bowel syndrome and almost 20% suffer from migraine headaches. Increased numbers of mast cells have been reported in interstitial cystitis. Mast cell activation, which is critical if these cells were to be implicated in this syndrome, has been investigated by electron microscopy, which definitively shows mast cell secretion. Recently, methylhistamine, the major metabolite of histamine, and the specific mast cell marker, tryptase, were shown to be significantly elevated in urine of interstitial cystitis patients. Bladder biopsies from 53 patients were analyzed blindly for the number and degree of activation of mast cells using 4 different stains for light microscopy, as well as electron microscopy. Controls included 16 patients with incontinence and chronic bacterial cystitis. Mast cells in controls were less than 10/mm.2 and were all nearly intact. Surprisingly, mast cells from 11 cancer patients averaged 50/mm.2 but almost all were intact. In contrast, mast cells from 26 interstitial cystitis patients averaged 40/mm.2 and more than 90% were activated to various degrees. Therefore, bladder mast cell activation is a characteristic pathological finding in at least a subset of patients with interstitial cystitis.
 ...
PMID:Activation of bladder mast cells in interstitial cystitis: a light and electron microscopic study. 786 1

High-intensity electrical stimulation of the trigeminal ganglion is accompanied by mast cell degranulation, vasodilatation, increased endothelial permeability and leakage of albumin from postcapillary venules within the dura mater. Overall, the histological appearance suggests an evolving sterile inflammatory response. This neurogenic inflammation within the meninges has been suggested as a model to explain the pain in migraine and cluster headache, and has been used to characterize the pharmacology of anti-migraine compounds. Using the rat model of neurogenic inflammation, the albumin extravasation ratio (stimulated : unstimulated side) in vehicle-treated animals in the dura and retina was 1.60 +/- 0.11 and 1.76 +/- 0.18, respectively (n = 10; values are mean +/- SEM). Pretreatment with sumatriptan (n = 9) produced a highly significant reduction in the ratio of extravasation within the dura to 1.10 +/- 0.06 (P = 0.002) and in the retina to 0.96 +/- 0.06 (P = 0.001), as did the neurokinin-1 receptor antagonist RP 67580 (n = 12) in the dura (1.04 +/- 0.11, P = 0.002) and retina (1.08 +/- 0.06, P = 0.001). These data demonstrate increased endothelial permeability and leakage of albumin not only in the dura but also in the retina. In a second stage we investigated possible extravasation in the human retina in acute migraine (n = 8) and cluster headache (n = 5) using fluorescein or indocyanine angiography. No increased endothelial permeability or leakage of dye could be found in the human retinal or choroidal vessels during headache attacks or in the headache-free interval in persons suffering from both migraine and cluster headache. These data raise the possibility that neurogenic inflammation is not a major factor in headache attacks in migraine or cluster headache.
 ...
PMID:Retinal plasma extravasation in animals but not in humans: implications for the pathophysiology of migraine. 967 75

Stress worsens certain disorders such as migraines or asthma, and has also been implicated in sudden myocardial arrest. It was previously shown that acute psychological stress by immobilization results in dura mast cell degranulation, an effect blocked by pretreatment with antiserum against corticotropin-releasing hormone (CRH). Moreover, CRH was recently shown to induce skin mast cell degranulation. The effect of psychological stress was investigated on rat cardiac mast cells, because their release of coronary constrictive and proinflammatory molecules contributes to myocardial ischemia and possibly arrhythmias. Immobilization of rats for 30 min induced maximal cardiac mast cell degranulation as evidenced by light and electron microscopy. This effect was inhibited by pretreatment with the "antiallergic" drug sodium cromoglycate (cromolyn), which is thought to act primarily through mast cell stabilization. Mast cell degranulation was also blocked by preincubation with antiserum against CRH and was partially inhibited by a CRH type-1 receptor selective antagonist. Sensory neuropeptides did not appear to influence this effect, but a nonpeptide neurotensin receptor antagonist blocked stress-induced cardiac mast cell degranulation. This finding supports the involvement of neuropeptide neurotensin which is present in the heart and is known to trigger mast cell degranulation. These results indicate acute stress could result in local CRH and nonpeptide neurotensin release which could contribute to myocardial pathophysiology through direct or indirect release of cardiac mast cell mediators.
 ...
PMID:A neurotensin receptor antagonist inhibits acute immobilization stress-induced cardiac mast cell degranulation, a corticotropin-releasing hormone-dependent process. 976 51

Cyclic vomiting syndrome is characterized by sudden episodes of vomiting and abdominal pain. It occurs primarily in children, is exacerbated by stress, and is often considered a migraine equivalent. Migraines have been linked to mast cells, which are often found close to neurons where they are activated by neuropeptides. We investigated the ultrastructural appearance of rat ileal brush border and mast cells following acute stress by immobilization. The effect of sulfated proteoglycans heparin and chondroitin sulfate was also tested on mast cell histamine secretion. Ileal brush border appeared intact in control animals, but was shorter and exhibited intercellular gaps after 30 min of acute immobilization stress. Mast cell activation in control rats was minimal, while stress induced obvious signs of activation as judged from disappearance of secretory granule electron dense contents. However, these intragranular changes were not accompanied by typical degranulation through exocytosis. Treatment of purified homogeneic rat peritoneal mast cells with 10(-4) M heparin or chondroitin sulfate 30 min prior to stimulation with 0.5 microg/ml compound 48/80 decreased histamine release by over 70% and 50% (P < 0.05), respectively. These results suggest the possible usefulness of chondroitin sulfate in conditions such as cyclic vomiting syndrome.
 ...
PMID:Stress-induced rat intestinal mast cell intragranular activation and inhibitory effect of sulfated proteoglycans. 1049 45

Mast cells derive from a distinct bone marrow precursor and mature in tissues under the influence of stem cell factor, nerve growth factor (NGF) and certain interleukins. Intracranial mast cells first appear in the meninges and are located perivascularly close to neurons. They can be activated by antidromic stimulation of the trigeminal nerve, as well as by acute immobilization stress. Substance P (SP) and corticotropin-releasing hormone (CRH) are particularly potent in stimulating mast cell release of vasoactive, inflammatory and nociceptive molecules. These findings have suggested that mast cells may be involved in neuroinflammatory conditions, such as migraines. In this study, dura mast cells were shown to have characteristics of connective tissue mast cells (CTMC) as they contained histamine, heparin and rat mast cell protease I (RMCP-I). Mast cells were localized close to SP-positive neurons immunocytochemically and mast cell-neuron contacts were also documented using scanning electron microscopy. Dura stimulated by SP and carbachol in situ released histamine. Preincubation of dura with estradiol slightly augmented histamine release by SP, an effect possibly mediated through estrogen receptors identified on dura mast cells. Acute stress by immobilization led to dura mast cell degranulation which was prevented by pretreatment with a neutralizing antibody to CRH or a CRH receptor antagonist. The present results further clarify the biology of intracranial mast cells and support their involvement in the pathophysiology of migraines which are precipitated or worsened by stress.
 ...
PMID:Morphological and functional demonstration of rat dura mater mast cell-neuron interactions in vitro and in vivo. 1059 82

Nerve fibres and mast cells are often described in close morphological and functional interactions in various organs such as the dura mater. The respective roles of mast cell activation and sympathetic impairment in cluster headache and migraine attacks have been repeatedly suggested. We have thus investigated the long-term effects of sympathectomy on mast cell morphology and content in the rat dura mater. Fifteen to 60 days after either sham, unilateral or bilateral superior cervical ganglionectomy, dura were removed for either histochemical or biochemical analysis. In the first case, they were fixed and mast cell heparin was stained by fluorescein isothiocyanate-conjugated avidin. Microscopic examination was followed by digital acquisitions using a tomographic process to assess mast cell density in the whole depth of the dura mater. Unilateral ganglionectomy induced a progressive and significant increase in mast cell density 15-60 days post-surgery in contralateral hemi-dura and 30 days post-surgery in ipsilateral hemi-dura. This increase was significant in both dura 60 days after bilateral ganglionectomy. Following perfusion with saline, we also examined the content of histamine and serotonin, pre-formed amines stored in mast cell granules. Biochemical analysis of dura serotonin and histamine content using high-pressure liquid chromatography and radioenzymatic assays, respectively, revealed under all conditions a serotonin tissue concentration lower than that of histamine. After sham ganglionectomy, the dura serotonin content increased from 15 to 60 days post-surgery, whereas the histamine content remained stable over the same period. After unilateral ganglionectomy, the histamine content increased progressively and significantly 30-60 days post-surgery in both hemi-dura, whereas the serotonin content became significantly different from that of sham only 60 days post-surgery in the ipsilateral dura. After bilateral ganglionectomy, the histamine level significantly increased in both hemi-dura 15-60 days post-surgery, whereas the serotonin level had significantly increased at 60 days post-surgery. These results clearly demonstrate, for the first time, a long-term trophic effect of sympathetic nerve degeneration on mast cells in the dura mater. Since mast cell activation has been described previously on the painful side of cluster headache patients during attack periods, we propose that the sympathetic impairment reported in these patients could be prominent, directly or indirectly inducing mast cell hyperplasia and changes in amine contents in the tissue concerned.
 ...
PMID:Long-term superior cervical sympathectomy induces mast cell hyperplasia and increases histamine and serotonin content in the rat dura mater. 1068 24


1 2 3 4 5 Next >>