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May 18, 2004Blood

Role of G protein–gated inwardly rectifying potassium channels in P2Y12 receptor–mediated platelet functional responses

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Key result

GIRK channel inhibitors SCH23390 and U50488H inhibited ADP- and low-dose thrombin-mediated platelet aggregation, indicating GIRK channels are important functional effectors of the P2Y12 receptor.

Population

Aspirin-treated and washed human platelets

Design

Preclinical

Authors

HSHaripriya ShankarThomas Jefferson UniversitySMSwaminathan MurugappanUniversity of MinnesotaSKSoochong KimChungbuk National University

Discussion

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Implication

GIRK inhibition may curb platelet aggregation; leaves open translation to human antithrombotic strategies.

Structured PICO

P
Population
Aspirin-treated and washed human platelets
I
Intervention
GIRK channel inhibitors (SCH23390 and U50488H)
O
Outcome
Platelet aggregation and functional responses (dense granule secretion, Akt phosphorylation, shape change, calcium mobilization, adenylyl cyclase inhibition)surrogate

GIRK channels are identified as important functional effectors of the P2Y12 receptor in human platelets, providing mechanistic insight into platelet activation.

Cite This Study

Shankar et al. (2004) studied this question. GIRK channel inhibitors (SCH23390 and U50488H) was evaluated on Platelet aggregation and functional responses. GIRK channel inhibitors SCH23390 and U50488H inhibited ADP- and low-dose thrombin-mediated platelet aggregation, indicating GIRK channels are important functional effectors of the P2Y12 receptor.

synapsesocial.com/papers/6a8985acb4e829b19bd44feahttps://doi.org/10.1182/blood-2004-01-0069
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Coordinated Signaling through Both G12/13 and Gi Pathways Is Sufficient to Activate GPIIb/IIIa in Human Platelets2002 · 123 citations
  2. 2Potentiation of Thromboxane A2-induced Platelet Secretion by Gi Signaling through the Phosphoinositide-3 Kinase Pathway2001 · 92 citations
  3. 3Evidence that neuronal G-protein-gated inwardly rectifying K+ channels are activated by G beta gamma subunits and function as heteromultimers.1995 · 309 citations
  4. 4Functional and Biochemical Evidence for G-protein-gated Inwardly Rectifying K+ (GIRK) Channels Composed of GIRK2 and GIRK32000 · 113 citations
  5. 5The K<sup>+</sup> channel inward rectifier subunits form a channel similar to neuronal G protein‐gated K<sup>+</sup> channel1996 · 90 citations