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)

The regulation of histamine release from oxyntic mucosa is complex because of two potential sources of histamine: mast cells and enterochromaffin-like (ECL) cells. A gastrin-responsive histamine pool was identified in the rat oxyntic mucosa two decades ago, but these ECL cells from the rat have not yet been isolated or characterized in vitro. In vivo studies in canine and human mucosa have been more difficult because of the high content of histamine in mast cells. Using enzyme-dispersed canine oxyntic mucosal cells, we have studied regulation of histamine release from a mast cell-depleted fraction prepared by sequential elutriation and density gradient. Histamine-like immunoreactivity was demonstrated, using peroxidase-anti-peroxidase immunohistochemistry. After short-term culture, histamine was released in response to gastrin, cholecystokinin, carbachol, and forskolin. Somatostatin potently and effectively inhibited the response to gastrin. The cultures used for these studies also contained somatostatin cells, and, furthermore, the response to gastrin was enhanced by incubation with monoclonal antibodies to somatostatin. The latter findings suggested that somatostatin was acting in these cultures by a paracrine route. This pattern contrasts with that obtained in previous studies of canine oxyntic mucosal mast cells.
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PMID:Regulation of histamine release from oxyntic mucosa. 128 99

Among the variety of signals stimulating pancreatic secretion, cholecystokinin (CCK) and related hormones are assumed to be responsible for modulating proteinase output. In some species, intraduodenal tryptic activity has to be abolished to demonstrate feedback-induced CCK release. The aim of this study was to investigate in vivo effects of modest inhibition of intraduodenal proteolytic enzymes on the secretion patterns of pancreatic enzymes and plasma CCK concentrations. Two inhibitors (Kunitz trypsin inhibitor and Bowman-Birk inhibitor) were applied. Intermittent sampling of plasma nd duodenal juice was performed during intraduodenal saline and inhibitor instillations in six healthy volunteers. Enzyme activities and concentrations were determined in the duodenal samples and expressed as percentage of basal values. Instillation of Kunitz trypsin inhibitor caused an increase in trypsin and the pancreatic secretory trypsin inhibitor (PSTI), without changes in plasma CCK. This result demonstrates, for the first time, that pancreatic exocrine secretion of trypsin and chymotrypsin is regulated by different mechanisms. Bowman-Birk inhibitor additionally stimulated the secretion of chymotrypsin and carboxypeptidase A and B and increased plasma CCK. Elastase 1 and amylase secretions were not increased by either instillations. Although the inhibitors have similar in vitro inhibition patterns, their in vivo effects are different. The nonparallel secretion of proteinases (trypsin, chymotrypsin and elastase 1) supports the view of a complex system involved in feedback regulation of human pancreatic exocrine secretion, including signals other than CCK.
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PMID:Proteinase inhibitors induce selective stimulation of human trypsin and chymotrypsin secretion. 859 48

The jejunal inflammation induced in rats by the nematode Nippostrongylus brasiliensis is followed by intestinal neuroimmune alterations including mast cell hyperplasia and nerve remodelling. On the other hand, cholecystokinin (CCK) plays a pivotal role in the regulation of intestinal motility. The aim of this study was to determine whether the intestinal motor response to CCK is altered 30 days after infection by N. brasiliensis. Thus, CCK-8 (50 microg kg(-1) intraperitoneally) disrupted the pattern of jejunal migrating myoelectric complexes for a longer time in postinfected rats (95.5 +/- 3.5 min) than in controls (48.1 +/- 5.1 min). This enhanced jejunal response was also found after oral administration of the potent releaser of endogenous CCK, soybean trypsin inhibitor. In contrast, no alteration of the inhibition of colonic motility by CCK administration was observed. The increased responsiveness of jejunal motility to CCK persisted after mast cell stabilisation or depletion but was prevented by atropine, devazepide and L-365260 (CCK-A and CCK-B receptor antagonists, respectively) and vagotomy. These results indicate that neuroimmune alterations after N. brasiliensis infection lead to an increased intestinal motility response to CCK that involves a cholinergic mediation, a vagal pathway and alterations in intestinal CCK-A and CCK-B receptors.
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PMID:Enhanced intestinal motor response to cholecystokinin in post-Nippostrongylus brasiliensis-infected rats: modulation by CCK receptors and the vagus nerve. 1129 94

Mast cells are involved in the pathogenesis of both allergies to food and inflammatory bowel disorders. In addition, there are several lines of evidence suggesting that mucosal mast cells also respond to intraluminal stimuli. Our aim was to identify neuroendocrine stimuli that could modify mucosal mast cell activity in the rat. Anaesthetized rats were prepared for duodenal perfusion and mast cell activation was measured by analysis of RMCP II concentration in the duodenal perfusate. Either buffered saline solution or a 5% ovalbumin hydrolysate (OVH) solution was infused into the duodenum. Subdiaphragmatic vagotomy or afferent ablation by intraluminal treatment with capsaicin diminished RMCP II concentration in basal conditions and significantly reduced the response to OVH, which in control animals induced a three-fold increase of the protease. The noradrenergic blockers phentholamine and propranolol significantly diminished RMCP II concentration in basal conditions and completely blocked the response to OVH. Intravenous infusion of cholecystokinin-related peptides also induced a response of mast cells. However, the response was different depending on the peptide. CCK-8 induced a slight increase of RMCP II, whereas both CCK-33 and gastrin induced a significant decrease in mast cell activity. These results show that intraluminal content modulates mucosal mast cell activity by complex mechanisms involving both nervous and endocrine pathway.
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PMID:Neuroendocrine control of intestinal mucosal mast cells under physiological conditions. 1187 52

Trichinella spiralis infection in rats induces hypermotility and an abnormal response to cholecystokinin (CCK) similar to motor disturbances observed in irritable bowel syndrome. Mast cell hyperplasia is also characteristic of this experimental model. The aim of our study was to correlate mast cell activity with the development of dysmotility and to demonstrate whether the mast cell stabilizer ketotifen [4-(1-methyl-4-piperidylidene)-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-10(9H)-one fumarate] could prevent the development of intestine hypermotility. Sprague-Dawley rats were infected with T. spiralis and, 5 days after infection, treated with the mast-cell stabilizer ketotifen (10 mg/kg/day). Twelve days after infection, intestinal spontaneous motor activity and response to CCK were evaluated by means of strain-gauge transducers. Immunohistochemistry for rat mast cell protease II (RMCPII), cyclooxygenase (COX)-2, and inducible nitric-oxide synthase (iNOS) was performed in intestinal specimens. In addition, RMCPII and myeloperoxidase were determined in serum. Infected control rats showed hypermotility, mast cell hyperplasia, increased RMCPII levels, increased myeloperoxidase, and overexpression of COX-2 and iNOS. In contrast, ketotifen-treated rats showed spontaneous intestinal motility and CCK response similar to the noninfected control rats. Mast cell hyperplasia and RMCPII were reduced in ketotifen-treated rats. Inflammatory parameters were less modified by ketotifen, but those animals that received the longest ketotifen treatment showed a slight amelioration in these parameters. These results indicate that mast cells are implicated in the development of hypermotility. The treatment with ketotifen prevented hypermotility and mast cell hyperplasia and diminished mucosal mast cell activity.
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PMID:Mast cell stabilizer ketotifen [4-(1-methyl-4-piperidylidene)-4h-benzo[4,5]cyclohepta[1,2-b]thiophen-10(9H)-one fumarate] prevents mucosal mast cell hyperplasia and intestinal dysmotility in experimental Trichinella spiralis inflammation in the rat. 1698 56

Giardia intestinalis is a significant cause of diarrheal disease worldwide. Infections in animal models have been shown to cause changes in gastrointestinal transit that depend on adaptive immune responses and are mediated, in part, through neuronal nitric oxide synthase. Nitric oxide is an inhibitory neurotransmitter, and we therefore investigated potential excitatory pathways that might be involved in the response to Giardia infection. Infected mice exhibited increased spontaneous and cholecystokinin (CCK)-induced contractions of longitudinal smooth muscle. In contrast, enhanced contractile responses were not observed in response to acetylcholine, 5-hydroxytryptamine, or the protease-activated receptor-1 agonist peptide TFFLR. Giardia-induced changes in smooth muscle function appear to be mediated primarily by mast cells, as both spontaneous and CCK-induced contractions were blocked by pretreatment with either ketotifen or compound 48/80. Together, these data support a model in which CCK release triggers mast cell degranulation, leading to increases in smooth muscle contractility. These contractions, coupled with nitric oxide-mediated muscle relaxation, promote intestinal transit and parasite elimination.
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PMID:Mast cell-mediated changes in smooth muscle contractility during mouse giardiasis. 1762 Mar 54

Pythons exhibit a doubling of heart rate when metabolism increases several times during digestion. Pythons, therefore, represent a promising model organism to study autonomic cardiovascular regulation during the postprandial state, and previous studies show that the postprandial tachycardia is governed by a release of vagal tone as well as a pronounced stimulation from nonadrenergic, noncholinergic (NANC) factors. Here we show that infusion of plasma from digesting donor pythons elicit a marked tachycardia in fasting snakes, demonstrating that the NANC factor resides in the blood. Injections of the gastrin and cholecystokinin receptor antagonist proglumide had no effect on double-blocked heart rate or blood pressure. Histamine has been recognized as a NANC factor in the early postprandial period in pythons, but the mechanism of its release has not been identified. Mast cells represent the largest repository of histamine in vertebrates, and it has been speculated that mast cells release histamine during digestion. Treatment with the mast cell stabilizer cromolyn significantly reduced postprandial heart rate in pythons compared with an untreated group but did not affect double-blocked heart rate. While this study indicates that histamine induces postprandial tachycardia in pythons, its release during digestion is not stimulated by gastrin or cholecystokinin nor is its release from mast cells a stimulant of postprandial tachycardia.
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PMID:Humoral regulation of heart rate during digestion in pythons (Python molurus and Python regius). 2242 67