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)

Systematic substitution of the natural L-amino acids in neurotensin by their D isomers reveals that the COOH-terminal portion of this tridecapeptide is required for binding to mast cell receptors: D-amino acid replacements from Pro10 through Leu13 substantially decrease that binding. Either blockage of the COOH-terminal carboxyl group as with N-methylamidation, or formation of a cyclic structure by the inclusion of a disulfide bond, a Cys2,13 substitution, markedly reduces the specific binding to mast cell receptor sites. Modifications in the NH2-terminal portion of neurotensin do not affect the binding to mast cells. However, D-Arg8 and D-Arg9 substitutions increase binding by factors of 5- to 6-fold. The hydroxyl group at position 3 or 11 is not essential for binding since Phe3 or Phe11 is equivalent to Tyr3 or Tyr11. The COOH-terminal penta- and hexapeptides are able to displace approximately 70% 125I-neurotensin relative to the intact peptide. Of 18 other biologically active peptides tested, only xenopsin, a naturally occurring COOH-terminal analog of neurotensin, and bradykinin effectively compete in the binding assay to an extent of 60 and 100%, respectively. Histamine, diphenhydramine, and noradrenaline are ineffective in this regard.
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PMID:Mast cell binding of neurotensin. II. Molecular conformation of neurotensin involved in the stereospecific binding to mast cell receptor sites. 19 4

The bovine splenic nerve trunk contains mast cells, ganglion cells, small intensely fluorescent (SIF) cells, and varicosities which exhibit a brilliant fluorescence characteristic for noradrenaline (NA) and dopamine (DA) after formaldehyde exposure. All these catecholamine-rich structures could contribute particles to isolated nerve vesicle fractions. Mast cells are recognized ultrastructurally by their large (300-800 nm) dense granules. SIF cells may be represented by cells and processes containing dense cored vesicles (120-140 nm) which are larger than the typical vesicles in axons and terminals. Terminal-like areas with typical large dense cored vesicles (LDV, 75 nm) and small dense cored vesicles (SDV, 45-55 nm) probably correspond to the fluorescent varicosities. The LDV constitute about 40% of all vesicles in terminal-like areas and terminals. Their staining properties indicate the presence of protein, phospholipids, and ATP. Tyramine depletes NA without loss of matrix density. The LDV can fuse with the terminal membrane, and released material outside omega profiles is interpreted to depict exocytosis. Large and small vesicles are easily distinguished from the very large mast cell granules and the moderately dense Schwann cell vesicles. Neither appear to contaminate the LDV fractions but the latter may contain a small population of SIF cell vesicles. Golgi vesicles from the Schwann cells mainly occur in the lighter zones of the gradient.
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PMID:Catecholamine-rich cells and varicosities in bovine splenic nerve, vesicle contents and evidence for exocytosis. 45 41

1. The effect of chemical denervation with 6-hydroxydopamine (6-OHDA) upon portal tract fibroblasts of dogs and rabbits was studied. 2. Denervation led to a significant increase in the density of portal tract fibroblasts both in the dog and in the rabbit. 3. Mast cells, present in the dog but not in the rabbit liver, were also significantly increased by denervation. 4. Noradrenaline depletion induced by reserpine did not increase the density of fibroblasts in the liver portal spaces of the dog. Mast cell density, however, was actually decreased when compared with control. 5. Continuous i.v. infusions of adenosine (10 micrograms kg-1h-1) to dogs totally prevented the effects of 6-OHDA-induced denervation upon fibroblast and mast cell densities in the portal space connective tissue. 6. It is concluded that the sympathetic nervous system is exerting a repressive effect on liver fibroblasts, as was found to occur in various other mammalian tissues. Mast cells, which are known to be activated in various pathological processes of fibrosis, appear to share with fibroblasts a modulating effect from the sympathetic nervous system. 7. The results strongly support the hypothesis of adenosine being the sympathetic trophic factor involved in the control of fibroblasts in the connective tissue of dog liver. A similar role for adenosine had previously been found in the dog saphenous vein.
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PMID:Effects of sympathetic denervation on liver fibroblasts: prevention by adenosine. 211 15

Changes in vascular tone brought about by electrical field stimulation were studied in isolated guinea-pig and monkey pial arteries, using stimulus intensities similar to, or weaker than, those usually utilized by other investigators. In the guinea-pig, excitation of the smooth muscle cells was easily induced, even at low intensity stimulus parameters. This contraction faded upon repeated stimulation. Certain characteristics indicated that the response was neurogenic with excitation of perivascular sympathetic nerve terminals, despite the fact that it persisted after treatment with guanethidine and phentolamine and was only little reduced by tetrodotoxin; surgical sympathectomy or pretreatment with reserpine abolished the response, whereas removal of endothelium or mast cell degranulation was without effect. Attempts were made to further characterize the substance released. It was probably not noradrenaline, neuropeptide Y, adenosine triphosphate, serotonin, histamine or acetylcholine. In the monkey, similar low intensity stimulus parameters induced a fully tetrodotoxin-sensitive contractile response, attributable to the release of noradrenaline alone. By a minor increase in stimulus intensity, tetrodotoxin-resistant contractions, probably due to direct smooth muscle activation, could easily be obtained in pial arteries from both species. Tests were also performed to elucidate whether a dilatation, caused by a neurogenic transmitter release, could be obtained in these vessels. In both species, however, only a tetrodotoxin-resistant response was found, even at weak stimulus intensities, in agreement with previous observations in vessels from several other species. The present data illustrate the need for a careful choice of stimulus parameters when vascular tonic responses upon electrical field stimulation are used as an index for neurogenic release. They also demonstrate that such a response may, indeed, be neurogenic despite marked resistance to tetrodotoxin.
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PMID:Characterization of the contractile and dilatory responses to electrical field stimulation in guinea-pig and monkey isolated pial arteries. 261 29

An in vivo model of the rat urinary bladder microcirculation has been developed and microcirculatory responses to agents which produce vasoconstriction, vasodilation, and macromolecular leakage have been characterized. The urinary bladder of anesthetized female Sprague-Dawley rats is exteriorized and positioned in a tissue bath with a single stay suture which does not penetrate the lumen of the bladder. All blood vessels and nerves from the animal remain intact. The tissue bath is filled with Krebs solution which is monitored and maintained at a temperature of 36 +/- 0.5 degrees and a pH of 7.4 +/- 0.5. In vivo television microscopy is used to monitor vascular diameter and flow changes and isothiocyanate-tagged bovine serum albumin fluorescence is used as an index of macromolecular leakage. Norepinephrine (10(-6) M) caused a statistically significant decrease in vascular diameters of both arterioles and venules while sodium nitroprusside (10(-7) M) significantly increased arteriolar and venular diameters, histamine (10(-4) M) caused no change in venular diameters but did induce a significant macromolecular leak from those vessels. Compound 48/80 (1 and 10 micrograms/ml) induced a significant dose-dependent macromolecular leakage from venules. However, only with the 10 micrograms/ml dose was there visually detectable mast cell degranulation. It is concluded that this rat urinary bladder model provides a stable, reproducible model of a smooth muscle microcirculatory bed in a controlled environment, which responds similarly to other microcirculations.
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PMID:The rat urinary bladder: vasoactivity and macromolecular leakage in a new model. 276 31

1. Using a previously established method of isolating an active-sodium-transport inhibitor (ASTI) from hypothalamic cell culture medium, the inhibitor was isolated and partially purified from sequential passages through Sephadex G-25 and h.p.l.c., and its effects on de-endothelialized rabbit aortic strips were investigated. 2. ASTI caused a cumulative concentration-dependent increase in tension which reversed slowly after wash, and the wash showed an identical effect on fresh strips. 3. Ouabain, used as a control, also caused a concentration-dependent increase in tension which reached a plateau at a concentration of 10 mmol/l. Both ouabain and ASTI caused a significant potentiation of the vasoconstrictor effect of noradrenaline at concentrations of 1 nmol/l-0.1 mmol/l. 4. Both ASTI and ouabain caused a significantly greater (P less than 0.01) calcium retention than control medium in aortic strips. 5. Incubation of ASTI with prolidase, chymotrypsin and carboxypeptidase A destroyed the vasoconstrictor effects as well as its inhibitory effects on sodium, potassium-dependent adenosine triphosphatase and sodium efflux from erythrocytes, but leucine aminopeptidase was ineffective. 6. These studies suggest that hypothalamic cells in culture release a peptidic inhibitor of active sodium transport which increases vascular reactivity, potentiates vasoconstrictor effects of noradrenaline and causes calcium retention.
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PMID:Calcium retention and increased vascular reactivity caused by a hypothalamic sodium transport inhibitor. 340 35

The intracerebroventricular injection of the mast cell degranulator, compound 48/80 (C48/80, 10 micrograms/kg), produced a marked behavioural syndrome in rats which included head and body shakes, paw tremor, excessive grooming, unusual posture and gait, mild diarrhoea, piloerection, extreme agitation and irritability to touch, sedation and catatonia. Fifteen minutes after C48/80, the histamine concentrations were decreased significantly in all brain regions examined, i.e. the cortex, cerebellum, midbrain, medulla oblongata-pons (MO-P) and hypothalamus. The noradrenaline (NA) concentrations were decreased in the cerebellum, hypothalamus and MO-P, whereas the dopamine (DA) content was decreased in the MO-P only. The concentrations of serotonin were not affected. As such, the behaviours following the acute degranulation of brain mast cells by C48/80 may result predominantly from the release of histamine and possibly NA and DA.
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PMID:The effects of intracerebroventricular administration of compound 48/80 on behaviour and regional brain amine concentrations in the rat. 370 80

1 The rank order of potency of six beta-adrenoceptor agonists as inhibitors of the anaphylactic release of histamine from fragments of passively sensitized human lung in vitro was (--)-isoprenaline greater than (--) -adrenaline greater than (+/-)-salbutamol greater than (--)-noradrenaline greater than R0363 greater than H133/22. 2 The beta-adrenoceptor antagonists, propranolol, atenolol and H35/25, blocked the response to both (--)-isoprenaline and (+/-)-salbutamol competitively. Each antagonist gave similar pA2 values with both agonists. pA2 values were consistently at the high end of the range expected for interaction at a beta 2-adrenoceptor. 3 Practolol did not antagonize isoprenaline in a competitive manner but was a competitive antagonist of salbutamol with a pA2 at the high end of the range expected for interaction at a beta 2-adrenoceptor. 4 Data obtained with agonists are consistent with the receptor being of the beta 2-subtype. Data obtained with antagonists indicate a consistently higher affinity for the receptor than observed for the beta 2-subtype in other tissues but do not suggest a novel beta-adrenoceptor subtype on the mast cell of the human lung.
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PMID:Characterization of the receptor mediating the antianaphylactic effects of beta-adrenoceptor agonists in human lung tissue in vitro. 616 1

The correlation between the binding of a beta-adrenoceptor antagonist, (--)[3H]-dihydroalprenolol (DHAP), and the adrenergic inhibition of histamine release by acetylcholine and by compound 48/80 was studied with isolated purified rat mast cells and in rat mast cell crude membrane fractions. Acetylcholine-evoked histamine release was inhibited by catecholamines, in the order isoprenaline greater than adrenaline greater than noradrenaline. Pretreatment of cells with (--)alprenolol antagonized the inhibitory effect of isoprenaline on acetylcholine-induced histamine release. 40/80-evoked histamine release was blocked by isoprenaline at significantly higher concentrations than those required to inhibit cholinergic histamine release. The inhibitory effect of isoprenaline was equally antagonized by preincubating mast cells with (--)alprenolol. Specific binding sites for DHAP have been demonstrated in rat mast cell membranes. The specific binding of DHAP was inhibited by adrenoceptor agonists and antagonists according to the stereospecificity of these compounds. A close correlation between the binding-inhibitory potency of various adrenergic compounds and the data obtained in the pharmacological experiments was found, thus indicating the presence of beta-adrenoceptors in rat mast cells.
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PMID:Presence of functionally active beta-adrenoceptors in rat mast cells. Correlation between (--)[3H]-dihydroalprenolol binding and inhibition of histamine release. 618 55

The variations of several biogenic amines in brown adipose tissue (BAT) during cold exposure were studied and their localization investigated with histological methods. The study of serotonin and its metabolite 5-HIAA suggests that BAT serotonin is mobilized during acute and chronic cold exposure. This amine was found to be principally stored, together with histamine, in mast cells. The mast cell number in BAT was doubled during cold adaptation, as was the histamine content of the tissue. Using radio-enzymatic assay and high pressure liquid chromatography, only small amounts of dopamine were found in BAT. Since no specific dopamine-storing structure was detected (for example SIF cells), this low amount of dopamine is probably the precursor pool for noradrenaline synthesis and is most likely stored in the noradrenergic innervation of the tissue. BAT is known to be sensitive to both exogenous serotonin and exogenous dopamine; according to our results serotonin could play a role in BAT regulation while the role of dopamine remains hypothetical.
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PMID:Localization of serotonin and dopamine in the brown adipose tissue of the rat and their variations during cold exposure. 620 Dec 16


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