Platelet activation following vascular injury involves multiple amplification steps. Thromboxane A2 (TXA2) amplifies platelet activation by binding the TP receptor. Which intracellular pathway does TP receptor activation utilise, and which is its primary effect on platelets?
- A Gs-coupled TP receptor → cAMP elevation → PKA → phosphorylation of GpIIb/IIIa → fibrinogen binding
- B Gq-coupled TP receptor → phospholipase C → IP3/DAG → Ca²⁺ release from dense tubular system + PKC activation → shape change and granule secretion ✓
- C Gi-coupled TP receptor → adenylyl cyclase inhibition → reduced cAMP → platelet activation
- D G12/13-coupled TP receptor → RhoA activation → MLCK phosphorylation → shape change exclusively
Correct answer: B. Gq-coupled TP receptor → phospholipase C → IP3/DAG → Ca²⁺ release from dense tubular system + PKC activation → shape change and granule secretion
Explanation
The thromboxane A2 receptor (TP receptor) couples predominantly to Gq and G12/13. Gq activation stimulates phospholipase C-beta, generating IP3 (releases Ca²⁺ from the dense tubular system) and DAG (activates PKC). The combined Ca²⁺/PKC signal drives platelet shape change, alpha and dense granule secretion, and inside-out activation of integrin GpIIb/IIIa to bind fibrinogen. Aspirin inhibits TXA2 synthesis by irreversibly acetylating COX-1. Prostacyclin (PGI2) from endothelium signals via Gs/cAMP to inhibit platelets — the physiological counterbalance.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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