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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0003320,
umls-concept:C0005270,
umls-concept:C0022642,
umls-concept:C0024880,
umls-concept:C0025914,
umls-concept:C0026809,
umls-concept:C0030685,
umls-concept:C0032172,
umls-concept:C0220781,
umls-concept:C0391871,
umls-concept:C0680255,
umls-concept:C1283071,
umls-concept:C1948023,
umls-concept:C1963578
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pubmed:issue |
2
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pubmed:dateCreated |
1988-3-25
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pubmed:abstractText |
Acetyl-CoA acetyltransferase (1-O-alkyl-sn-glycero-3-phosphocholine) is a key enzyme in paf-acether biosynthesis. Its immunological activation as related to paf-acether formation was investigated in mast cells derived from mouse bone marrow. The action of ketotifen, a prophylactic anti-asthma drug, on the antigen-induced activation of acetyltransferase and on the release of paf-acether and beta-hexosaminidase was studied in mast cells. Mast cells were sensitized with dinitrophenyl-specific monoclonal IgE and preincubated for 15 min at 37 degrees C with various concentrations of ketotifen or vehicle prior to challenge with dinitrophenyl coupled to bovine serum albumin (40 ng/ml). Acetyltransferase activity and mediator formation and release were measured. Ketotifen inhibited dose dependently the antigen-induced paf-acether formation and release, beta-hexosaminidase release and acetyltransferase stimulation. The IC50 values were 20.0 +/- 4.4, 11.8 +/- 6.2, 8.8 +/- 3.8 and 20.5 +/- 3.4 microM (mean +/- S.E.M., n = 3) respectively. Mast cells were preincubated with 50 microM ketotifen for 15 min at 37 degrees C then washed prior to antigen challenge. The release of paf-acether and beta-hexosaminidase and the stimulation of acetyltransferase were inhibited by 90.0 +/- 15.0, 91.0 +/- 15.0 and 88.0 +/- 11.0% (n = 3) respectively. In addition, Ca2+ entry was inhibited by 100% as assessed from Quin-2 fluorescence. Thus, the release of a preformed granular enzyme beta-hexosaminidase is inhibited by ketotifen together with the enzymatic formation of a newly formed mediator.(ABSTRACT TRUNCATED AT 250 WORDS)
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0014-2999
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
144
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
133-9
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:2963750-Acetyltransferases,
pubmed-meshheading:2963750-Animals,
pubmed-meshheading:2963750-Cell Survival,
pubmed-meshheading:2963750-Ketotifen,
pubmed-meshheading:2963750-Mast Cells,
pubmed-meshheading:2963750-Mice,
pubmed-meshheading:2963750-Mice, Inbred BALB C,
pubmed-meshheading:2963750-Mice, Inbred C57BL,
pubmed-meshheading:2963750-Platelet Activating Factor,
pubmed-meshheading:2963750-beta-N-Acetylhexosaminidases
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pubmed:year |
1987
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pubmed:articleTitle |
Ketotifen inhibits paf-acether biosynthesis and beta-hexosaminidase release in mouse mast cells stimulated with antigen.
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pubmed:affiliation |
INSERM U.200, Université Paris-Sud, France.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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