| Title |
Investigation of cyclooxygenase and signaling pathways involved in human platelet aggregation mediated by synergistic interaction of various agonists
|
|---|---|
| Published in |
Drug Design, Development and Therapy, July 2015
|
| DOI | 10.2147/dddt.s84335 |
| Pubmed ID | |
| Authors |
Nadia Khan, Ahsana Dar Farooq, Bassem Sadek |
| Abstract |
In the present study, the mechanism(s) of synergistic interaction of various platelet mediators such as arachidonic acid (AA) when combined with 5-hydroxytryptamine (5-HT) or adenosine diphosphate (ADP) on human platelet aggregation were examined. The results demonstrated that 5-HT had no or negligible effect on aggregation but it did potentiate the aggregation response of AA. Similarly, the combination of subeffective concentrations of ADP and AA exhibited noticeable rise in platelet aggregation. Moreover, the observed synergistic effect of AA with 5-HT on platelets was inhibited by different cyclooxygenase (COX) inhibitors, namely ibuprofen and celecoxib, with half maximal inhibitory effect (IC50) values of 18.0±1.8 and 15.6±3.4 μmol/L, respectively. Interestingly, the synergistic effect observed for AA with 5-HT was, also, blocked by the 5-HT receptor blockers cyproheptadine (IC50=22.0±7 μmol/L), ketanserin (IC50=152±23 μmol/L), phospholipase C (PLC) inhibitor (U73122; IC50=6.1±0.8 μmol/L), and mitogen activated protein kinase (MAPK) inhibitor (PD98059; IC50=3.8±0.5 μmol/L). Likewise, the synergism of AA and ADP was, also, attenuated by COX inhibitors (ibuprofen; IC50=20±4 μmol/L and celecoxib; IC50=24±7 μmol/L), PLC inhibitor (U73122; IC50=3.7±0.3 μmol/L), and MAPK inhibitor (PD98059; IC50=2.8±1.1 μmol/L). Our observed data demonstrate that the combination of subthreshold concentrations of agonists amplifies platelet aggregation and that these synergistic effects largely depend on activation of COX/thromboxane A2, receptor-operated Ca(2+) channels, Gq/PLC, and MAPK signaling pathways. Moreover, our data revealed that inhibition of COX pathways by using both selective and/or non-selective COX inhibitors blocks not only AA metabolism and thromboxane A2 formation, but also its binding to Gq receptors and activation of receptor-operated Ca(2+) channels in platelets. Overall, our results show that PLC and MAPK inhibitors proved to inhibit the synergistic activation of platelets by several/multiple agonists. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| India | 1 | 33% |
| Unknown | 2 | 67% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 2 | 67% |
| Practitioners (doctors, other healthcare professionals) | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 16 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 3 | 19% |
| Other | 2 | 13% |
| Student > Doctoral Student | 2 | 13% |
| Student > Ph. D. Student | 2 | 13% |
| Student > Bachelor | 1 | 6% |
| Other | 3 | 19% |
| Unknown | 3 | 19% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 3 | 19% |
| Medicine and Dentistry | 3 | 19% |
| Agricultural and Biological Sciences | 2 | 13% |
| Nursing and Health Professions | 1 | 6% |
| Unspecified | 1 | 6% |
| Other | 2 | 13% |
| Unknown | 4 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 March 2020.
All research outputs
#14,914,476
of 25,373,627 outputs
Outputs from Drug Design, Development and Therapy
#792
of 2,268 outputs
Outputs of similar age
#130,560
of 277,610 outputs
Outputs of similar age from Drug Design, Development and Therapy
#51
of 157 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 40th percentile – i.e., 40% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,268 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.1. This one has gotten more attention than average, scoring higher than 64% of its peers.
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We're also able to compare this research output to 157 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 66% of its contemporaries.