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- Title
Involvement of cyclooxygenase, phospholipase C and MAP kinase pathways in human platelet aggregation mediated by the synergistic interaction of adrenaline and PAF.
- Authors
Saeed, Sheikh A.; Rasheed, Huma; Hoodbhoy, Zahra A.; Pasha, Simeen R.; Mapara, Zohair; Kumar, Haresh; Shah, Bukhtiar H.
- Abstract
This study was conducted to examine the mechanism(s) of synergistic interaction of adrenaline and platelet-activating factor (PAF) mediated human platelet aggregation. We found that platelet aggregation mediated by subthreshold concentrations of PAF (5-8 nM) plus adrenaline (0.5-2 μM) was inhibited by both α[sub 2]-adrenoceptor blocker (yohimbine) and PAF receptor antagonist (WEB2086). While examining the role of the downstream signalling pathways, we found that this synergism was inhibited by calcium channel blockers, verapamil, and diltiazem. In addition, platelet aggregation by co-addition of adrenaline and PAF was also inhibited by very low concentrations of phospholipase C (PLC) inhibitor (U73122; IC[sub 50] = 0.2 μ[sub M]), the MAP kinase inhibitor, PD98059 (IC[sub 50] = 3 μ[sub M]) and cyclooxygenase (COX-1) inhibitors including indomethacin (IC[sub 50 ]= 0.25 μ[sub M]), flurbiprofen (IC[sub 50] = 0.7 μ[sub M]) and piroxicam (IC[sub 50] = 7 μ[sub M]). However, the COX-2 inhibitor, nimesulide, was also effective in inhibiting the aggregation. The inhibitors of tyrosine kinase (genistien) and phosphatidylinositol 3-kinase inhibitor (wortmannin) had no significant effects on platelet aggregation. These data suggest that the synergistic effect of adrenaline and PAF on human platelet aggregation is receptor-mediated and involves the activation of PLC/calcium, COX and MAP kinase signalling pathways.
- Subjects
BLOOD platelet aggregation; ADRENALINE; PLATELET-derived growth factor; PHYSIOLOGY
- Publication
Inflammopharmacology, 2001, Vol 9, Issue 1/2, p147
- ISSN
0925-4692
- Publication type
Article
- DOI
10.1163/156856001300248425