Linked Life Data

9359523

Source:http://linkedlifedata.com/resource/pubmed/id/9359523

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1997-12-9
pubmed:abstractText
The exposure of human platelets to prostaglandin H2 analogue (PGH2, U46619) induces homologous desensitization and a concomitant adenylate cyclase (AC) sensitization. We demonstrate the involvement of phospholipase C (PLC) in this enzyme sensitization. Pre-incubation of platelets with neomycin, a PLC activity inhibitor, prevented AC sensitization but not PGH2/thromboxane (Tx)A2 receptor desensitization. PGH2/TxA2 receptor desensitization, although necessary, is not sufficient to induce AC sensitization, since neomycin, which prevents AC sensitization, failed to prevent receptor desensitization. Inositol phosphate formation, determined in parallel, was also inhibited. Interestingly, no guanylate cyclase sensitization was noted, suggesting a specific relationship between PGH2/TxA2 receptor desensitization and AC sensitization. In addition, using alkaline phosphatase, a dephosphorylating enzyme, and the tyrosine kinase inhibitor erbstatin, we examined the role of phosphorylation-dephosphorylation on AC sensitization. Effectively, alkaline phosphatase, which has no effect by itself, enhances the cAMP production triggered by prostacyclin in control but not in desensitized platelets. In contrast, erbstatin failed to modify this synthesis, indicating the non-involvement of tyrosine kinase pathway in this process. Our results indicate that the AC sensitization was mediated by PLC and also suggest the participation of other mechanisms, including phosphorylation-dephosphorylation processes. This specific enzyme sensitization may be relevant for the in vivo modulation of platelet activation, in different thrombotic diseases with an increased TxA2 generation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0007-1048
pubmed:author
pubmed:issnType
Print
pubmed:volume
99
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
190-6
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Signal transduction involved in the platelet adenylate cyclase sensitization associated with PGH2/TxA2 receptor desensitization.
pubmed:affiliation
Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur-INSERM U285, Paris, France.
pubmed:publicationType
Journal Article