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)

The isolated activation segment (asA) from pig pancreatic procarboxypeptidase A was studied by 1H-n.m.r. spectroscopy over a wide range of solution conditions. Isolated asA shows many characteristics of compactly folded globular proteins, such as the observation of perturbed positions for resonances from methyl groups, alpha-carbon atoms, histidine residues and the tyrosine residue. The single tyrosine residue (Tyr-70) exhibits a very high pKa, and both histidine and tyrosine residues show slow chemical modification (deuteration and iodination). In contrast, asA shows rapid NH exchange. Analysis of the spectra by pH titration and nuclear Overhauser effects revealed several residue interactions. Quantitative analysis of deuterium and tritium exchange allowed the assignment of the histidine C-2-H resonances to their respective residues in the sequence. His-66, the closest to the sites of proteolytic attack in the proenzyme, is shown to be the most accessible to solvent in procarboxypeptidase A. It was also shown that asA is thermally very stable ['melting' temperature (Tm) 88 degrees C] and requires a high urea concentration for denaturation (6.25 M, at pH 7.5). Evidence is presented for some degree of conformational flexibility in the premelting range, a feature that could be ascribed to the preponderance of helical secondary structure and to the lack of disulphide bridges. The free solution structure of asA is probably unchanged when it binds to carboxypeptidase A.
 ...
PMID:1H-n.m.r. studies of the isolated activation segment from pig procarboxypeptidase A. 232 81

The identification of transglutaminase in the growth-factor-dependent mouse mast cell line PT18 was accomplished through its characteristic catalytic properties (specificity, calcium dependency, and inhibition by iodoacetamide); and by both immunoprecipitation and Western blot analysis using affinity purified antibody. The enzymatic activity in these cells increased in association with the release of histamine from the cells induced by an IgE-dependent mechanism or by exposure to the ionophores A23187 or Br-x537A. The increase in transglutaminase activity was paralleled by a marked increase in the level of protein-bound gamma-glutamylhistamine, determined in radiolabeled form in mast cells that were either metabolically labeled with [3H]histidine or incubated with [3H]histamine before degranulation. The highest level of bound gamma-glutamylhistamine was found in the immunologically stimulated cells. Enzymatic activity and the gamma-glutamyl derivative were associated primarily with the cells, both before and after stimulation. Separation of gamma-glutamylhistamine in a proteolytic digest of these cells was carried out using a combination of ion exchange chromatography and high performance liquid chromatography. The gamma-glutamyl compound was identified and quantitated through the enzymatic production of histamine with the use of gamma-glutamylamine cyclotransferase, an enzyme specific for the disassembly of gamma-glutamylamines.
 ...
PMID:Activation of transglutaminase and production of protein-bound gamma-glutamylhistamine in stimulated mouse mast cells. 241 84

A new 28 amino acid peptide, we recently isolated from the venom of the bumblebee Megabombus pennsylvanicus. has been characterized. The peptide, Met-Cys-Ile-Cys-Lys-Asn-Gly-Lys-Pro-Leu-Pro-Gly-Phe-Ile-Gly-Lys-Ile-Cys- Arg-Lys-Ile-Cys-Met-Met-Gln-Gln-Thr-His(NH2), has been named bumblebee mast cell degranulating (MCD) peptide due to its ability to degranulate rat peritoneal mast cells, and its resemblance to the bee venom MCD peptide. Bumblebee MCD peptide, unlike bombolitins, the other mast cell degranulating heptadecapeptides of bumblebee venom, is not lytic and releases histamine at a dose as low as 0.05 micrograms/ml (1.6 X 10(-8) M).
 ...
PMID:Amino acid sequence of bumblebee MCD peptide: a new mast cell degranulating peptide from the venom of the bumblebee Megabombus pennsylvanicus. 242 Dec 65

When peritoneal resident cells (PRCs) of genetically mast cell-deficient WBB6F1-W/Wv mice were cultured in vitro for 5 h at 37 degrees C, their histidine decarboxylase [HDC, L-histidine carboxylase, E.C. 4.1.1.22] activity increased 10-fold. Since inhibitors for energy production and mRNA and protein syntheses inhibited this increase of HDC activity, it appeared to represent de novo synthesis of the enzyme, i.e., induction. This increase was followed by an increase in the amount of histamine in the culture medium of the cells, indicating that histamine synthesized by the induced HDC was not stored in the cells but was quickly released. Mast cells were not involved in the HDC induction, because the extents of HDC induction in PRCs of W/Wv and wild type +/+ mice were similar. The removal of T cells with anti-Thy-1,2 antibody and complement from the PRCs did not affect the HDC induction, but the removal of phagocytes decreased the induction to one-tenth in spite of a 2-fold increase in the proportion of B cells in the PRCs. After separation of the PRCs into adherent and non-adherent fractions, the increase in HDC activity was found to be associated with the adherent fraction that was mostly positive to esterase staining. These results suggest that HDC was induced in peritoneal macrophages.
 ...
PMID:In vitro increase of histidine decarboxylase activity and release of histamine by peritoneal resident cells of mast cell-deficient W/Wv mice; possible involvement of macrophages. 245 55

In the present study we investigated the specificity of the releasing effects of compound 48/80 (48/80) for mast cell vs. neuronal histamine (HA) from hypothalamic slices. In addition, we investigated the selectivity of the releasing effects of 48/80 for HA compared to other neurotransmitters. Brain slices from W/W mice, a genetic mutant devoid of mast cells, and +/+ mice, its normal counterpart, were used. Hypothalamic slices were labeled with [3H]HA or [3H]histidine. 48/80 elicited similar degrees of release of [3H]HA from both mouse strains, irrespective of the label used. In addition, 48/80 produced marked increases in the efflux of dopamine (DA), serotonin (5-HT), norepinephrine (NE) and modest increases in the efflux of acetylcholine (ACh). These effects were concentration-dependent and the magnitude of release varied with the transmitter examined (DA greater than NE greater than 5-HT much greater than ACh = HA). Transmitter efflux induced by 48/80 was not altered by low calcium concentrations or by tetraethylammonium; whereas, release evoked by electrical stimulation was reduced and increased, respectively, by these treatments. In mouse striatal slices preloaded with [3H]DA, 48/80 induced an initial increase in [3H]DA efflux, followed by a marked increase in the efflux of its metabolite, [3H]-3,4-dihydroxyphenylacetic acid. Nomifensine failed to inhibit, whereas reserpine pretreatment reduced 48/80-induced efflux of 3H. In summary, these results indicate that the incubation of hypothalamic slices with [3H]HA or [3H]histidine labels HA neurons selectively and that 48/80 (10-100 micrograms/ml) releases HA from nonmast cell compartments.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Monoamine release by compound 48/80 from nonmast cell compartments in mouse brain slices. 246 Jun 15

The acid proteases, pepsin, rennin and cathepsin D, were shown to generate mast cell histamine releasing peptides (HRP) when incubated with the albumin fraction of mammalian plasmas. Significant histamine release was observed using less than 1 microliter equivalent of pepsin-treated plasma. Histamine release was rapid, dependent on calcium and energy, and accompanied by degranulation. The major HRP present in pepsin-treated human and canine plasma was identified as H-Ile-Ala-Arg-Arg-His-Pro-Tyr-Phe-OH whereas that from rat plasma had valine substituted for isoleucine. Cathepsin D-treated BSA gave rise to the human octapeptide (above) as well as to an extended decapeptide with H-Tyr-Glu- at the N-terminus. These peptides were apparently derived from one region of serum albumin, residues 139 to 149 of the human, canine, or bovine sequence. We hypothesize that cathepsin D, released from leukocyte lysosomes, might generate HRP during the delayed phase of an inflammatory response.
 ...
PMID:Structures of histamine-releasing peptides formed by the action of acid proteases on mammalian albumin(s). 247 9

Five structurally related heptadecapeptides rich in hydrophobic amino acids have been discovered in the venom of the bumblebee Megabombus pennsylvanicus. We have named them bombolitin I (Ile-Lys-Ile-Thr-Thr-Met-Leu-Ala-Lys-Leu-Gly-Lys-Val-Leu-Ala-His-Val-NH2 ), bombolitin II (Ser-Lys-Ile-Thr-Asp-Ile-Leu-Ala-Lys-Leu-Gly-Lys-Val-Leu-Ala-His-Val-NH2 ), bombolitin III (Ile-Lys-Ile-Met-Asp-Ile-Leu-Ala-Lys-Leu-Gly-Lys-Val-Leu-Ala-His-Val-NH2 ), bombolitin IV (Ile-Asn-Ile-Lys-Asp-Ile-Leu-Ala-Lys-Leu-Val-Lys-Val-Leu-Gly-His-Val-NH2 ), and bombolitin V (Ile-Asn-Val-Leu-Gly-Ile-Leu-Gly-Leu-Leu-Gly-Lys-Ala-Leu-Ser-His-Leu-NH2 ). Bombolitins are structurally and functionally very similar. They lyse erythrocytes and liposomes, release histamine from rat peritoneal mast cells, and stimulate phospholipase A2 from different sources. The threshold dose is 0.5-2.5 micrograms/ml depending on the peptide and the bioassay. Bombolitin V is as potent as the well-known melittin in lysing guinea pig erythrocytes (ED50 = 0.7 microgram/ml = 4 X 10(-7) M) and is 5 times more potent than mastoparan in causing mast cell degranulation, making it one of the most potent degranulating peptides discovered so far (ED50 = 2 micrograms/ml = 1.2 X 10(-6) M). The bombolitins represent a unique structural class of peptides but they have the same biological properties as melittin (from honeybees), mastoparan (wasps, hornets, and yellow jackets), and crabrolin (European hornets). This unusual circumstance (peptides with different amino acid sequences having the same biological properties) may be a manifestion of their amphiphilic nature, a property these peptides have in common.
 ...
PMID:Bombolitins, a new class of mast cell degranulating peptides from the venom of the bumblebee Megabombus pennsylvanicus. 257 59

Parasympathetic innervation of the respiratory tract of nasal mucosa plays an important role in the pathogenesis of chronic hypertrophic non-allergic rhinitis (C.H.N.A.R.), the vidian nerve providing the main parasympathetic nerve supply to respiratory mucosa. The present study investigates the effect of vidian nerve resection in 22 patient with intractable C.H.N.A.R. on histamine content and formation and on the number of mast cells and their degranulation in the respiratory tract. Samples were taken from respiratory mucosa for histamine and histidine-decarboxylase assay, and for microscopic observations for mast cell density and degranulation index, before and 12-24 months after vidian nerve resection. Neurectomy of the vidian nerve completely cured the clinical symptomatology, evaluated by rhinoreomanometry, and also significantly decreased both the high histamine levels and histidine-decarboxylase activity in patients with C.H.N.A.R. The density and degranulation index of mast cells were also significantly lower after surgery. These data suggest a relationship between cholinergic activity and the secretory response of mast cells and indicates a correlation between the parasympathetic nerve supply and chronic hyperthrophic non-allergic rhinitis. The significant reduction in mast cell density, histamine levels and histidine-decarboxylase activity also lends support to the hypothesis that the parasympathetic nerve supply plays a role in the regulation of mast cell histamine.
 ...
PMID:Vidian nerve resection, histamine turnover and mucosal mast cell function in patients with chronic hypertrophic non-allergic rhinitis. 259 75

A novel inhibitor of angiotensin-converting enzyme (ACE) derived from tuna muscle, Pro-Thr-His-Ile-Lys-Trp-Gly-Asp (tuna AI), was chemically synthesized, and its biological properties were investigated. Synthetic tuna AI was found to be chemically and biologically indistinguishable from the native one. Tuna AI inhibited rabbit lung ACE non-competitively with Ki values of 1.7 and 5.7 microM with substrates, hippuryl-L-histidyl-L-leucine and angiotensin I, respectively. This peptide (5.3 microM) also doubled the effect of bradykinin in the contraction of isolated guinea pig ileum. The peptide did not show zinc chelating activity and carboxypeptidase A inhibitory activity. Thus, tuna AI was found to be a unique ACE inhibitory peptide with non-competitive manner, differing from many naturally occurring peptide ACE-inhibitors.
 ...
PMID:Biological properties of angiotensin-converting enzyme inhibitor derived from tuna muscle. 261 45

The amino acid sequence has been determined of a mouse mucosal mast cell protease isolated from the small intestines of mice infected with Trichinella spiralis. The active protease contains 226 residues. Those corresponding to the catalytic triad of the active site of mammalian serine proteases (His-57, Asp-102, and Ser-195 in chymotrypsin) occur in identical positions. A computer search for homology indicates 74.3% and 74.1% sequence identity of the mouse mast cell protease compared to those of rat mast cell proteases I and II (RMCP I and II), respectively. The six half-cystine residues in the mouse mast cell protease are located in the same positions as in the rat mast cell proteases, cathepsin G, and the lymphocyte proteases, suggesting that they all have identical disulfide bond arrangements. At physiological pH, the mouse and rat mucosal mast cell proteases have net charges of +3 and +4, respectively, as compared to +18 for the protease (RMCP I) from rat connective tissue mast cells. This observation is consistent with the difference in solubility between the mucosal and connective tissue mast cell proteases when the enzymes are extracted from their granules under physiological conditions.
 ...
PMID:Amino acid sequence of a mouse mucosal mast cell protease. 270 64


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>