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)

Besides apamin, the structurally related MCD peptide (mast cell degranulating peptide; peptide 401) is another centrally acting peptide from bee venom. In contrast to apamin, it is hardly neurotoxic upon intravenous injection in mice. Following intraventricular injection, as little as 0.3 microgram/animal produce convulsions and respiratory arrest in mice. The clinical picture differs from that elicited by apamin, and apamin is about 10 times more potent than MCD peptide when given intraventricularly. Apamin and MCD peptide injected into the spinal cord of rats in nanogram amounts, produce circumscript hyperexcitation lasting more than one day, however with complete recovery following sublethal doses. Local apamin poisoning differs from local tetanus (elicited by the same way) by its faster time course.
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PMID:Neurotoxicity of apamin and MCD peptide upon central application. 59 41

The synthesis by conventional methods of the following three peptides is described: MCD(8-11) Boc-His(Trt)-Val-Ile-Lys(Z) (III) MCD(5-7) Boc-Cys(SiPr)-Lys(Z)-Arg(Tos) (IV) and MCD(1-4) Boc-Ile-Lys(Z)-Cys(Trt)-Asn(Mbh) (V). These peptides are fragments of the mast cell degranulating peptide from bee venom. The purity of the fragments synthesized was examined by thin-layer chromatography, amino acid and elementary analysis. Including the fragments Boc-Lys(Z)-Ile-Cys(SiPr)-Gly-Lys(Z) (I) and Boc-Pro-His(Trt)-Ile-Cys(Trt)-Arg(Tos) (II), which were described earlier, the synthesis of the mast-cell-degranulating peptide on a polyethylene-asparagine support appears possible.
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PMID:[Basic peptides in bee venom, III. Synthesis of peptide fragments from the sequence of the mast-cell-degranulating peptide (author's transl)]. 85 9

Both the bee venom toxin, mast cell degranulating peptide (MCD peptide) and the mamba toxin dendrotoxin I are potent central convulsants. The two specific receptor sites for these two types of polypeptide toxins are in allosteric interaction in brain membranes. Occupation of the dendrotoxin I binding site (KI = 0.4 nM) prevents binding of the 125I-MCD peptide to its own receptor (KI = 0.23 nM). This inhibition is of the non-competitive type. Autoradiography has shown that a high enough dendrotoxin I concentration (30 nM) prevented binding of 125I MCD peptide to all brain structures where specific receptors had been identified. A lower concentration of the mamba toxin led to a nearly selective inhibition of MCD peptide binding to the hippocampal region which is responsible for the convulsant properties of the 2 types of polypeptide toxins.
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PMID:Two potent central convulsant peptides, a bee venom toxin, the MCD peptide, and a snake venom toxin, dendrotoxin I, known to block K+ channels, have interacting receptor sites. 243 87

The binding sites of dendrotoxin I, mast cell degranulating peptide, and beta-bungarotoxin are thought to be associated with neuronal K+ channels. The different binding sites seem to reside on the same molecular assembly as each toxin can allosterically inhibit the binding of the others. Affinity chromatography on a beta-BTX Aca 22 affinity column has shown that there is an heterogeneous population of dendrotoxin I binding proteins. Two subtypes were separated: DTXI binding proteins with low affinity for beta-BTX (60-70% of total) and DTXI binding proteins with high affinity for beta-BTX (30-40% of total). Binding of 125I-DTXI and 125I-MCD to the former subtype is inhibited by beta-BTX with a low affinity (IC50 = 560 nM), while inhibition at the latter subtype occurs with a high affinity (IC50 = 10-16 nM). The DTXI binding subtype with low affinity for beta-BTX contains most (85-90%) of the binding sites for 125I-MCD.
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PMID:Existence of different populations of the dendrotoxin I binding protein associated with neuronal K+ channels. 245 6

Studies of azide inhibition of peptide hydrolysis catalyzed by cobalt(II) carboxypeptidase A identify two anion binding sites. Azide binding to the first site (KI = 35 mM) inhibits peptide hydrolysis in a partial competitive mode while binding at the second site (KI = 1.5 M) results in competitive inhibition. The cobalt electronic absorption spectrum is insensitive to azide binding at the first site but shows marked changes upon azide binding to the second site. Thus, azide elicits a spectral change with new lambda max (epsilon M) values of 590 (330) and 540 nm (190) and a KD of 1.4 M, equal to the second kinetic KI value for the cobalt enzyme, indicating that anion binding at the weaker site involves an interaction with the active-site metal. Remarkably, in the presence of the C-terminal products of peptide or ester hydrolysis or carboxylate inhibitor analogues, anion (e.g., azide, cyanate, and thiocyanate) binding is strongly synergistic; thus, KD for azide decreases to 4 mM in the presence of L-phenylalanine. These ternary complexes have characteristic absorption, CD, MCD, and EPR spectra. The absorption spectra of azide/carboxylate inhibitor ternary complexes with Co(II)CPD display a near-UV band between 305 and 310 nm with epsilon M values around 900-1250 M-1 cm-1. The lambda max values are close to the those of the charge-transfer band of an aquo Co(II)-azide complex (310 nm), consistent with the presence of a metal azide bond in the enzyme complex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interaction of anions with the active site of carboxypeptidase A. 283 74

P401 (also known as mast cell degranulating protein, MCD) is a minor component of honeybee venom. Its primary structure is related to that of apamin. We have studied the structure of P401 in solution by high-resolution two-dimensional 1H-NMR spectroscopy. Almost all the backbone proton resonances have been assigned by sequential assignment strategy. Analysis of NOEs shows that P401 has a conformation very similar to that of apamin. N-terminal residues Ile-1-Cys-5 are in an extended conformation and residues His-13-Asn-22 on the C-terminus are in an alpha-helical structure. These two secondary structural elements are connected by two tight turns.
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PMID:Structure of P401 (mast cell degranulating peptide) in solution. 323 81

The preparation of a pure, monoiodinated derivative of mast cell-degranulating peptide (MCD peptide), the mast cell-degranulating peptide from bee venom, has enabled us to identify binding sites in rat brain membranes that have a high affinity and specificity for this peptide. These binding sites are evenly distributed throughout the brain and copurify with synaptic membranes. Saturation-binding curves, determined by rapid centrifugation or filtration assays, indicate a single population of sites with a concentration of 200 fmol/mg membrane protein in partially fractionated, lysed brain membranes. Dissociation constants of 150 and 140 pM were calculated for the iodinated and native peptides, respectively. These binding sites are probably associated with the neurotoxic action of MCD peptide in the central nervous system. No similar binding sites have been identified in peripheral tissue preparations, and other polycationic mast cell-degranulating agents including compound 48/80 show no such specificity. Specific modification of the primary amines, arginine residues, or disulfide bridges of MCD peptide results in a complete loss of binding activity. Other components of bee venom show specificity for the MCD peptide-binding site, suggesting that a class of neurotoxins in bee venom (possibly including secapin and tertiapin, but not apamin) share the specific action of MCD peptide on the central nervous system.
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PMID:The characterization of high-affinity binding sites in rat brain for the mast cell-degranulating peptide from bee venom using the purified monoiodinated peptide. 650 Dec 83

A light and electron microscopic study of the evolution of acute eruptive guttate psoriasis vulgaris (AEGP) following penicillin-treated streptococcal throat infection is presented. The earliest recognizable changes, distinguished in clinically normal psoriatic skin (CNPS) from patients with psoriasis of 2 days' duration, comprised mast cell degranulation (Type I MCD), a vascular pattern showing endothelial cell gaps in postcapillary venules and postcapillary venules with endothelial cell hypertrophy and compressed lumen as well as epidermal involvement with punctiform spongiotic areas (PSAs). These early dermal and epidermal changes suggest that Type I MCD represents a primary morphologic event. Inflammatory infiltrate of mononuclear cells and exocytosis of mononuclear cells into the PSAs appeared when the concomitant overt psoriasis was 5-21 days old, and these changes were persistent in psoriatic lesions (PLs) of 2 days' duration. They are suggested to be precursors of overt psoriasis. In 2-day-old PLs, MCD (Types I and II) was a prominent feature. It was associated with (1) more extensive vascular changes, (2) inflammatory infiltrate of mononuclear cells and scanty polymorphonuclear leukocytes, (3) epidermal hyperplasia, and (4) migration of a few polymorphonuclear leukocytes through the epidermis with formation of Munro microabscesses in parakeratotic areas of stratum corneum. From the morphologic viewpoint, the progression from 2-day-old to fully evolved PLs seemed basically to be quantitative. The demonstration of MCD as a salient feature in the evolution of AEGP may have future therapeutic and preventive implications for psoriasis.
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PMID:Dermal and epidermal involvement in the evolution of acute eruptive guttate psoriasis vulgaris. 651 70

The solid phase synthesis of mast degranulating peptide (MCD peptide) raised the possibility of preparing analogs and examining the pharmacology and the proposed role of this peptide as a potential agent in allergy and inflammation. MCD peptide, a cationic 22-amino acid residue peptide with two disulfide bridges, causes mast cell degranulation and histamine release at low concentrations and has anti-inflammatory activity at higher concentrations. Because of these unique immunologic properties, MCD peptide may serve as a useful tool for studying secretory mechanisms of inflammatory cells such as mast cells, basophils, and leukocytes, leading to the design of compounds with therapeutic potential.
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PMID:Mast cell degranulating (MCD) peptide: a prototypic peptide in allergy and inflammation. 1044 3

We have investigated the effects on mast cell binding and the histamine-releasing activity of l-alanine substitutions for the five lysine residues and the proline residue in the MCD peptide (1) sequence. All synthesized analogues Ala(2) (2), Ala(6) (3), Ala(11) (4), Ala(12) (5), Ala(17) (6), and Ala(21) (7) showed a loss of histamine release compared to the parent MCD peptide 1. The order of decreased potency was 1 > 6 > 7 > 4 > 2 > 3 > 5. The alanine-substituted analogues showed a 5- to 6-fold decrease in histamine release for analogues 6, 7, and 4 and a 10-fold decrease for analogue 2. A more significant loss was observed in analogue 3 with a 75-fold loss of activity. The greatest loss of activity was observed with alanine substituting for proline in position 12. This analogue 5 showed a 130-fold loss of histamine release compared to the parent peptide 1. The ability of each analogue to interact with the FcepsilonRIalpha subunit of the human mast cell receptor was analyzed by competitive binding of the fluorescent peptide 1 and the alanine analogues using fluorescence polarization. The binding affinities of analogues 4, 6, and 7 for the mast cell receptor were less than the affinity of the native peptide 1. Analogues 2, 3, and 5 showed an increase in binding affinity, with analogue 5 showing the highest increase compared to the native peptide 1. The order of increased affinity was 5 > 3 > 2 > 1 > 4, 6, 7. On the basis of these results, the possibility that analogue 5 inhibits peptide 1-stimulated histamine release was examined. We found that peptide 5 did not inhibit histamine release by peptide 1. The analogues 2, 3, and especially analogue 5 may be useful leads toward study of agents that prevent binding of IgE to mast cell receptors.
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PMID:Histamine-releasing activity and binding to the FcepsilonRI alpha human mast cell receptor subunit of mast cell degranulating peptide analogues with alanine substitutions. 1282 39


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