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)

Non-immunologic and immunologic stimulation of mast cells have been compared. Non-immunologic stimulation relys heavily on cellular Ca, is unaffected by neuraminidase treatment, shows a rapid inactivation, and elicits no increase in the incorporation of 3H-methyl groups into the lipid fraction. In contrast, stimulation by immunologic agents relys primarily on extracellular Ca, is inhibited by neuraminidase treatment, shows a comparatively slow rate of inactivation, and causes a significant increase in the incorporation of 3H-methyl groups into the lipid fraction. We found no evidence of cross-inactivation or desensitization between immunologic and non-immunologic agents. However, pretreatment of mast cells with neurotensin desensitized them to subsequent stimulation by compound 48/80. Our results support the hypothesis that immunologic and non-immunologic agents activate exocytotic mast cell secretion via separate mechanisms.
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PMID:Mast cell secretion: differences between immunologic and non-immunologic stimulation. 243 14

1. Human skin mast cells, unlike other human mast cells so far studied, released histamine in a concentration-related manner in response to substance P, vasoactive intestinal peptide (VIP) and somatostatin (1 microM to 30 microM). In contrast, eledoisin, physalaemin, neurokinin A, neurokinin B, calcitonin gene-related peptide (CGRP), neurotensin, bradykinin and Lys-bradykinin induced negligible histamine release. 2. The low histamine releasing activity of physalaemin, eledoisin, neurokinin A and neurokinin B relative to substance P suggests that the human skin mast cell activation site is distinct from the tachykinin NK-1, NK-2 or NK-3 receptors described in smooth muscle. 3. The relative potencies of substance P and its fragments SP2-11, SP3-11, SP4-11 and SP1-4 in releasing histamine from human skin mast cells suggests that both the basic N-terminal amino acids and the lipophilic C-terminal portion of substance P are essential for activity. 4. Peptide-induced histamine release, like that induced by compound 48/80, morphine and poly-L-lysine, is rapid, reaching completion in 10-20 s, is largely independent of extracellular calcium but requires intact glycolysis and oxidative phosphorylation. 5. The substance P analogue, [D-Pro4,D-Trp7,9,10] SP4-11 (SPA), not only reduced substance P-induced histamine release in a concentration-related manner but also inhibited that induced by VIP, somatostatin, compound 48/80, poly-L-lysine and morphine but not anti-IgE. 6. The similar characteristics of histamine release induced by substance P, VIP, somatostatin, compound 48/80, poly-L-lysine and morphine suggest that they share a common pathway of activation-secretion coupling distinct from that of IgE-dependent activation. Furthermore, the ability of human skin mast cells to respond to basic non-immunological stimuli including neuropeptides may reflect a specialised function for these cells.
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PMID:Characterization of neuropeptide-induced histamine release from human dispersed skin mast cells. 246 82

Intracarotid infusions of neurotensin (NT) into the isolated, perfused head of rats trigger concentration-dependent histamine and 5-hydroxytryptamine (5-HT) release from the perfused organ. The secretory event was accompanied by a concentration-dependent rise in perfusion pressure and facilitation of edema formation. The three NT effects were markedly reduced in heads derived from rats pretreated with high doses of compound 48/80 to produce mast cell depletion. The vasoconstrictor response to NT was greatly attenuated by the 5-HT receptor antagonist methysergide but unaffected by antihistaminic drugs. The results were interpreted as an indication that NT stimulates histamine and 5-HT release from mast cells of the rat perfused head. The results also suggest that the vasoconstrictor response to NT in the rat head is mediated by mast cell 5-HT. The potentiation of edema formation by NT was attributed to the action of mast cell mediators (most likely histamine and 5-HT) released by NT on microvessels.
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PMID:Release of mast cell mediators, vasoconstriction and edema in the isolated, perfused head of the rat following intracarotid infusion of neurotensin. 258 Nov 66

Bolus injections of neurotensin (NT) in the rat perfused heart elicited a transient, dose-dependent histamine release. The histamine releasing effect of NT appears to be independent of the heart rate and coronary perfusion pressure and it was not influenced by atropine, propanolol, prazosin, methysergide, ketanserin, indomethacin, morphine, lidocaine or by removal of the atria. However, it was potentiated by adenosine, inhibited by sub-stimulatory concentrations of NT and the mast cell membrane stabilizing drug cromoglycate but was unaltered by the calcium antagonist verapamil. The absence of calcium in the heart perfusate suppressed the histamine releasing effect of NT. These results suggest that the histamine releasing effect of NT in the rat heart results from a direct effect on ventricular mast cells and is calcium-dependent.
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PMID:Characterization of the histamine releasing effect of neurotensin in the rat heart. 258 Dec 31

In an attempt to elucidate mechanisms underlying the irradiation-induced decrease in regional cerebral blood flow (rCBF) in primates, hippocampal and visual cortical blood flows of rhesus monkeys were measured by hydrogen clearance, before and after exposure to 100 Gy, whole-body, gamma irradiation. Systemic blood pressures were monitored simultaneously. Systemic arterial plasma histamine and neurotensin levels were determined preirradiation and postirradiation. Compared to control animals, the irradiated monkeys exhibited an abrupt decline in systemic blood pressure to 23% of the preirradiation level within 10 min postirradiation, falling to 12% by 60 min. A decrease in hippocampal blood flow to 32% of the preirradiation level was noted at 10 min postirradiation, followed by a slight recovery to 43% at 30 min and a decline to 23% by 60 min. The cortical blood flow for the same animals showed a steady decrease to 29% of the preirradiation levels by 60 min postirradiation. Animals given the mast cell stabilizer disodium cromoglycate and the antihistamines mepyramine and cimetidine before irradiation did not exhibit an abrupt decline in blood pressure but displayed a gradual decrease to a level 33% below preirradiation levels by 60 min postirradiation. Also, the treated, irradiated monkeys displayed rCBF values that were not significantly different from the nonirradiated controls. The plasma neurotensin levels in the irradiated animals, treated and untreated, indicated a nonsignificant postirradiation increase above control levels. However, the postirradiation plasma histamine levels in both irradiated groups showed an increase of approximately 1600% above the preirradiation levels and the postirradiation control levels. These findings implicate histamine in the postirradiation hypotension, but not necessarily in the direct responsibility for the decrease in regional cerebral blood flow seen immediately postirradiation in the primate.
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PMID:Effect of disodium cromoglycate (DSCG) and antihistamines on postirradiation cerebral blood flow and plasma levels of histamine and neurotensin. 289 22

Intravenous injections of neurotensin (NT) (0.5, 1 and 2 nmoles kg-1) evoked dose-dependent increases in histaminemia and hematocrit, and marked hypotensive effect, in anesthetized rats. The increase of plasma histamine was rapid in onset (within sec), peak plasma histamine being reached in less than 2 min. The decline of plasma histamine was gradual and almost complete 15 min after injection of NT. The hematocrit increased slowly, maximum values being obtained 5-10 min after injection of NT, and it persisted throughout the period of observation. The hypotensive effect of NT was rapid in onset and of prolonged duration. Compound 48/80, a well known histamine liberator and mast cell depletor, produced variations of blood pressure, of hematocrit and of plasma histamine very similar to those elicited by NT. Pretreatment of rats with cromoglycate, a well known mast cell stabilizer, or with dexamethasone, inhibited markedly the changes of histaminemia, of hematocrit and of blood pressure evoked by NT and compound 48/80. The results clearly suggest that the effects of NT on blood pressure and on vascular permeability in rats are mediated to some extent by mast cell histamine. Hexamethonium, a ganglion blocker, inhibited slightly the effect of NT on histaminemia but it did not block NT-induced changes of hematocrit. However, the hypotensive effect of NT was severely blocked in hexamethonium-treated rats. These results were interpretated as an indication that hexamethonium prevents NT-induced hypotension not merely by reducing the mobilization of mast cell histamine by NT but most likely by interfering with the mechanism by which NT and/or its mast cell mediators produce their effects on blood pressure.
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PMID:Influence of various drugs on the variations of blood pressure, hematocrit and plasma histamine caused by neurotensin and compound 48/80 in rats. 613 90

1. Neurotensin stimulated histamine release and granule extrusion when applied to isolated rat peritoneal mast cells. 2. This secretory response was prevented by the removal of calcium or energy and was not accompanied by the release of lactic dehydrogenase. 3. The secretory response produced by neurotensin was prevented by prior treatment of mast cells with cromoglycate. 4. The intravenous injection of neurotensin into anaesthetized rats produced a rapid and significant increase in the level of blood histamine that was dependent upon the dose of neurotensin. 5. Treatment of rats with compound 48/80, 24 hr before neurotensin, abolished the elevation in blood histamine caused by neurotensin. The intravenous injection of cromoglycate 1-2 min before neurotensin greatly reduced the response to neurotensin. 6. The intradermal injection of neurotensin (0.03-30 p-mole) increased capillary permeability in rats pre-treated intravenously with Evans Blue. This response was abolished by the antihistamine, diphenhydramine. Increasing the dose of neurotensin to 300 p-mole partially overcame this inhibition by diphenhydramine. 7. Our results demonstrate that neurotensin can elicit an exocytotic secretory response from isolated rat peritoneal mast cells and elevate histamine levels in blood. It is suggested that some of neurotensin's physiological effects may be due to stimulation of mast cell secretion.
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PMID:Neurotensin stimulates exocytotic histamine secretion from rat mast cells and elevates plasma histamine levels. 617 20

Cardiac output (CO) and blood flow to major organs were investigated in pentobarbital-anesthetized rats using 85Sr and 141Ce labelled microspheres (MS) of 15 microns diameter injected into the left ventricle. Changes in organ blood flow and CO were measured after intraventricular dextran (3.4 mumol/kg/min) and intravenous neurotensin (NT) at two different rates, 2.5 nmol/kg/min and 0.125 nmol/kg/min. Dextran, known to give anaphylactoid response in rats, reduced the mean arterial pressure (MAP) from 118 +/- 17 to 55 +/- 8 mmHg (p less than 0.001) concomitant with a 56% decline in CO and significant decreases in blood flow to most organs. At 2.5 nmol/kg/min, NT caused a pattern of changes in MAP, CO and organ blood flow similar to that obtained with dextran, and thus consistent with an indirect response via mast cell stimulation. NT injected at 0.125 nmol/kg/min resulted in a significant increase (30%) in blood flow to the small intestine (p less than 0.01) without changes in MAP or CO. Vascular resistance decreased by 30% in the small intestine (p less than 0.01) and by 20% in the large intestine (p less than 0.05). The results show that circulating NT, at concentrations below those eliciting hypotension, enhances intestinal blood flow without significant changes in other organs.
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PMID:Neurotensin-induced increase in intestinal blood flow in the anesthetized rat. 618 52

The mast cell degranulating capacity of neurotensin and three of its fragments was examined. In Tyrode solution (137 mM NaCl, 2.7 mM KCl, 0.4 mM NaH2PO4, 1.4 mM CaCl2, 1 mM MgCl2, 10 mM Hepes, 5.6 mM glucose, pH 7.4), neither intact neurotensin nor its C-terminal tripeptide (Tyr-Ile-Leu) caused any release of histamine. Concentrations of neurotensin exceeding 10(-4)M did cause histamine release but through lysis of the cells. The C-terminal hexa- and octapeptides of neurotensin (Arg-Arg-Pro-Tyr-Ile-Leu and Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu, respectively) induced a non-cytolytic release of histamine with the latter peptide being more active (ED50 = 90 microM for the hexapeptide and 13 microM for the octapeptide). This release was not affected by the C-terminal tripeptide. It was found to be calcium-dependent and was inhibited by the anti-allergic drug, disodium cromoglycate. Phosphatidylserine did not enhance release of histamine and saturation of the immunoglobulin E (IgE) receptors did not inhibit it.
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PMID:Structure-activity relationship in the mast cell degranulating capacity of neurotensin fragments. 618 72

Neurotensin (NT) evoked a transient, dose-dependent histamine release (ED50 170 ng ml-1) from the rat perfused heart. Histamine release by NT occurred within seconds and lasted less than 2 min. The histamine releasing effect of NT was followed by a dose-dependent increase of the perfusion pressure and a slight tachycardia. The histamine releasing effect of NT was completely abolished in hearts derived from rats pretreated for 3 days with high doses of compound 48/80. The coronary vasoconstrictor effect of NT was increased in hearts derived from compound 48/80-pretreated rats. The mast cell inhibitor cromoglycate markedly inhibited NT-induced histamine release without affecting the coronary vasoconstrictor effect of NT. The histamine releasing effect of NT was inhibited, while its coronary vasoconstrictor effect was markedly potentiated, in hearts derived from rats pretreated with the antiallergic and antiinflammatory steroid dexamethasone. The increase of perfusion pressure evoked by NT was not modified by antihistamine drugs. Infusions of exogenous histamine (10(-6)-10(-5) g ml-1) caused a dose-dependent coronary vasodilation in the rat perfused heart. The results suggest that NT stimulates histamine release from cardiac mast cells. These results together with those obtained in previous studies suggest that mast cell mediators (particularly histamine and serotonin) are unlikely to be responsible for the coronary vasoconstrictor effect of NT in the rat perfused heart.
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PMID:Neurotensin stimulates histamine release from the isolated, spontaneously beating heart of rats. 620 39


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