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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We know that the mast cell or basophil degranulation and the release of chemical mediators such as histamine may play an important role in inducing immediate type allergic reactions. In this experiment, employing purified rat peritoneal mast cells (RPMC) the degranulation pattern of RPMC and percent release of histamine from RPMC by pharmacologic (compound 48/80, kallikrein or peptidoglycan) or allergic (IgE-anti IgE complex) stimuli were examined. The inhibitory effects of catecholamine (isoproterenol), an adenylate cyclase stimulator, methylxanthine (IBMX: 3-isobutyl-1-methyl-xanthine), a phosphodiesterase inhibitor and chemical mediators (histamine, serotonin, bradykinin) on compound 48/80-induced RPMC degranulation and also those of catecholamine, methylxanthine and chemical mediators on IgE-anti IgE complex-induced histamine release from RPMC were tested. Compound 48/80-induced RPMC degranulation was remarkably inhibited not only by treatment with isoproterenol and IBMX, but also by treatment with histamine. It was not, however, inhibited by serotonin or bradykinin. The inhibitory effect of histamine on compound 48/80-induced RPMC degranulation was blocked by pretreatment with H2-antagonist (cimetidine), but not by H1-antagonist (diphenhydramine). The cyclic adenosine 3',5'-monophosphate (cAMP) content of RPMC was significantly increased by pretreatment with histamine as well as isoproterenol and IBMX. These facts suggest that cAMP acts as a regulator or modulator of the RPMC degranulation and the histamine release from mast cells and that the inhibitory effect induced by histamine may be related to the H2-receptor existing on the surface of mast cells.
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PMID:[Studies on the degranulation and histamine release of purified rat peritoneal mast cells. The inhibitory effect of histamine and other chemicals]. 247 72

A series of substance P (SP)- and bradykinin (BK)-related peptides have been compared for their histamine-releasing activities on rat peritoneal mast cells. Some of these peptides only differed in the N-acetylation of the N-terminal arginine residue or by the removal of charged residue at the N-terminal. The aim was to examine the role of the N-terminal positive charges in the histamine-releasing activity of compounds that are selective for the SP receptor (named NK-1) or for the B2 type bradykinin receptor. Only compounds with positive charges at the N-terminal caused non-cytotoxic histamine release from rat mast cells. It is suggested that SP- and BK-related peptides caused histamine release by a mechanism which appeared to be non-specific and not related to the activation of mast cell NK-1 or B2 receptors, respectively. Our results show that NK-1 agonists or B2 antagonists devoid of histamine-releasing activity, which could be of potential use in the clinic, can be obtained by removing the positively charged N-terminal aminoacids or by N-acetylation of the N-terminal arginine.
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PMID:Role of the N-terminal arginine in the histamine-releasing activity of substance P, bradykinin and related peptides. 247 72

In this review, only a few questions concerning the mechanism(s) of action of sodium cromoglycate in asthma have been considered. The large number of cells and mediator pathways where sodium cromoglycate may have pharmacological effects are depicted. In addition to its mast cell effect, sodium cromoglycate is also inhibitory to macrophages, eosinophils, monocytes and platelets, which are all important components in the inflammatory response of asthma. From studies with bradykinin and sulphur dioxide it is also known that the drug can block afferent discharges along non-myelinated nerves. Although the ability of sodium cromoglycate to block late phase responses and acquired hyper-reactivity is not questioned, to what extent its therapeutic efficacy can be accounted for by actions on these leukocytes and reflex pathways is not known. When administered to patients with asthma, sodium cromoglycate results in symptomatic improvement, but there is still much to be learned about its mode of action.
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PMID:Reflections on the mechanism(s) of action of sodium cromoglycate (Intal) and the role of mast cells in asthma. 251 46

The effect of a variety of non IgE-mediated stimuli on histamine release from mast cells from different locations is described. Sensory neuropeptides are shown to resemble other polycationic compounds in preferentially activating mast cells from the rat while having a limited effect on human mast cells, except possibly those from skin. Similar results were obtained with the putative non-adrenergic, non-cholinergic neurotransmitter ATP, thereby questioning the role of neuronal mast cell activation in allergy and inflammation. Bradykinin also acted selectively against rat cells while complement-derived and formylmethionyl peptides were effective against human basophils and cutaneous mast cells. The latter results may indicate a role for the skin cell in local inflammatory responses involving complement activation and in host resistance to bacterial infection. Rat mast cells and human basophils were most responsive to hyperosmolar challenge but significant effects were obtained from human pulmonary mast cells obtained by bronchoalveolar lavage. The latter cells may thus be implicated in exercise-induced asthma. The plasma substitute dextran was a specific secretagogue for the rat while morphine sulphate largely induced histamine release from human cutaneous mast cells. The latter result may account for anaphylactoid reactions to the opiate. In total these data emphasize the functional heterogeneity of mast cells from different locations and highlight the particular pharmacological properties of the skin mast cell in man.
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PMID:Non-IgE-mediated mast cell stimulation. 251 51

Human bronchial epithelial cells were isolated from macroscopically normal bronchi obtained from lobectomy specimens. Cells were grown in nutrient F12 medium, and after the third or fourth subculture they were stimulated with arachidonic acid, histamine, leukotrienes (LT) C4, D4, or E4, prostaglandin (PG) D2, anti-IgE, acetylcholine, bradykinin, or phorbol myristate acetate (PMA). Neither mast cell mediators (i.e., histamine, LTC4, LTD4, LTE4, or PGD2) nor anti-IgE stimulated the release of arachidonic acid metabolites from the epithelial cells. However, arachidonic acid, acetylcholine, bradykinin, and PMA stimulated the release of 15-hydroxyeicosatetraenoic acid (15-HETE) as major and prostaglandin E2 (PGE2) as minor products. The maximal release of 15-HETE and PGE2 occurred in 1 h with arachidonic acid stimulation and in 2 h with other stimuli. Arachidonic acid at 30 microM caused the release of 258 +/- 76 ng and 29 +/- 15 ng (n = 12) of 15-HETE and PGE2, respectively, from 10 x 10(6) epithelial cells, whereas acetylcholine, bradykinin, or PMA caused the release of approximately 2- to 10-fold less 15-HETE and PGE2. These results demonstrate that human bronchial epithelial cells selectively generate 15-HETE as the predominant arachidonic acid product and PGE2 as a minor metabolite. The role of bronchial epithelial cells and their mediators in the pathogenesis of bronchial hyperresponsiveness needs further study.
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PMID:Release of 15-hydroxyeicosatetraenoic acid (15-HETE) and prostaglandin E2 (PGE2) by cultured human bronchial epithelial cells. 251 53

N-alpha-[(S)-1-carboxy-3-phenylpropyl]-L-lysyl-L-proline (MK-0521) is a new non-sulfhydryl-containing angiotensin converting enzyme (ACE) inhibitor. The present investigation describes its ACE and other enzymes inhibitory properties and compares it to those of captopril, MK-421 and MK-422 in vitro. MK-0521 inhibited rat pulmonary ACE by 50% (IC50) at a concentration of 3 nM and was 6.13 times more potent than captopril. The IC50 values of MK-421 and MK-422 against ACE were 2,000 nM and 3.5 nM, respectively. MK-0521 had practically no inhibitory activities against carboxypeptidase A, carboxypeptidase B, leucine aminopeptidase, papain, pepsin and trypsin. The kinetic study on the inhibitory activity of M-0521 against ACE using Lineweaver-Burk plots indicated that MK-0521 exerted competitive ACE inhibition. The dialysis study conducted on the ACE-MK-0521 complex revealed that the inhibitory effect of MK-0521 against ACE was reversible. In the guinea pig ileum, MK-0521 potentiated the contractile effect of bradykinin and depressed the contractile effect of angiotensin I. These effects on bradykinin and angiotensin I were 33.11 and 2.63 times more potent than that of captopril, respectively. The present results suggest that MK-0521 may show a potent hypotensive effect in vivo.
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PMID:[Inhibitory effect of N-alpha-[(S)-1-carboxy-3-phenylpropyl]-L-lysyl-L-proline (MK-0521) on angiotensin converting enzyme in vitro]. 254 78

Plasma extravasation responses to silver nitrate (AgNO3), histamine, 5-hydroxytryptamine (5-HT), bradykinin and prostaglandin E1 (PGE1) in the abdominal skin, hindpaw ankle joint and subplantar region of rats have been investigated using the Evans blue dye leakage technique. All substances tested produced plasma extravasation and combination of low doses (5 x 10(-10) mol) of either histamine or bradykinin with PGE1 (5 x 10(-10) mol) exhibited potentiation of responses of all regions. Responses to AgNO3 (1 x 10(-6) mol) were significantly reduced by the H1 receptor antagonist, mepyramine, only in the abdominal skin, but the H2 receptor antagonist metiamide reduced the responses at subplantar and ankle joint regions. Indomethacin significantly reduced the AgNO3 responses at the ankle joint only, but aprotinin reduced it at the other two regions. In rats pretreated with a combination of all antagonists the residual plasma extravasation response to AgNO3 was very small, indicating that the response could be almost totally accounted for by the combined actions of mast cell amines, kinins and prostanoids. The finding that prostanoids played a major role in the plasma extravasation response of the rat ankle joint to AgNO3 indicated that this model would be useful for the screening of non-steroidal anti-inflammatory drugs.
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PMID:Mediators of the plasma extravasation response to silver nitrate in the rat skin, subplantar region and ankle joint. 256 64

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.
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PMID:Biological properties of angiotensin-converting enzyme inhibitor derived from tuna muscle. 261 45

[Thi5,8,D-Phe7]bradykinin caused hind-paw edema and degranulation of isolated peritoneal mast cells in a dose-dependent manner. Pretreatment with diphenhydramine/methysergide or compound 48/80 completely suppressed the edematous response caused by [Thi5,8,D-Phe7]bradykinin, whereas bradykinin-induced hind-paw swelling was only partially inhibited by diphenhydramine and methysergide pretreatment; the residual response was significantly further depressed by [Thi5,8,D-Phe7]bradykinin. Neither the bradykinin- nor [Thi5,8,D-Phe7]bradykinin-induced edematous response was significantly affected by aspirin or BW755C. The mast cell degranulation caused by [Thi5,8,D-Phe7]bradykinin and bradykinin was inhibited by gangliosides but not by heparin. These results suggest that the edematous response elicited by [Thi5,8,D-Phe7]bradykinin was mainly due to the actions of mediators released by the degranulation of mast cells. Unlike bradykinin, [Thi5,8,D-Phe7]bradykinin was devoid of a direct exudation-promoting effect but exerted an antagonistic effect on the direct effect of kinin. If the influence of mast cells degranulation could be minimized, [Thi5,8,D-Phe7]bradykinin could be used as a tool to evaluate the role of kinin in the edematous response in inflammation.
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PMID:Edematous response caused by [Thi5,8,D-Phe7]bradykinin, a B2 receptor antagonist, is due to mast cell degranulation. 264 May 60

A carboxypeptidase activity was recently identified in highly purified human lung mast cells and dispersed mast cells from skin. Using affinity chromatography with potato-tuber carboxypeptidase inhibitor as ligand, mast cell carboxypeptidase was purified to homogeneity from whole skin extracts. The purified enzyme yielded a single staining band of approximately 34,500 D on SDS-PAGE. Carboxypeptidase enzyme content estimated by determination of specific activity, was 0.5, 5, and 16 micrograms/10(6) mast cells from neonatal foreskin, adult facial skin, and adult foreskin, respectively. Human mast cell carboxypeptidase resembled bovine carboxypeptidase A with respect to hydrolysis of synthetic dipeptides and angiotensin I, but was distinguished from carboxypeptidase A in its inability to hydrolyze des-Arg9 bradykinin. The amino acid composition of human mast cell carboxypeptidase was similar to the composition of rat mast cell carboxypeptidase. The amino-terminal amino acid sequence of mast cell carboxypeptidase demonstrated 65% positional identity with human pancreatic carboxypeptidase B, but only 19% with human carboxypeptidase A. Thus, human mast cell carboxypeptidase is a novel member of the protein family of zinc-containing carboxypeptidases, in that it is functionally similar but not identical to bovine carboxypeptidase A, but has structural similarity to bovine and human pancreatic carboxypeptidase B.
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PMID:Human mast cell carboxypeptidase. Purification and characterization. 270 24


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