Biochemistry · Lipid Chemistry (Sphingolipids, Eicosanoids, Ketogenesis)

Thromboxane A2 (TXA2) and prostacyclin (PGI2) have opposing effects on platelet aggregation and vascular tone. Which statement correctly describes the mechanism of this physiological antagonism?

  • A TXA2 activates Gs in platelets (raising cAMP), while PGI2 inhibits Gs in vascular endothelium (lowering cAMP)
  • B TXA2 is synthesised by endothelial cells to inhibit platelet aggregation; PGI2 is platelet-derived and causes vasoconstriction
  • C Both act via the same COX-1 product but with opposing receptor affinity, creating a competitive balance
  • D TXA2 activates TP receptors (Gq/G12) in platelets raising IP3/DAG/Ca2+; PGI2 activates IP receptors (Gs) in platelets and endothelium raising cAMP and inhibiting aggregation/causing vasodilation
Correct answer: D. TXA2 activates TP receptors (Gq/G12) in platelets raising IP3/DAG/Ca2+; PGI2 activates IP receptors (Gs) in platelets and endothelium raising cAMP and inhibiting aggregation/causing vasodilation

Explanation

TXA2, produced by platelet COX-1/thromboxane synthase, binds TP receptors coupled to Gq (activating PLC → IP3 → Ca2+ → platelet shape change and granule release) and G12/13 (Rho kinase → cytoskeletal contraction). PGI2, produced by endothelial COX/prostacyclin synthase, binds IP receptors coupled to Gs → adenylyl cyclase → cAMP → PKA, which phosphorylates and inactivates MLCK and thrombin receptor signalling, inhibiting platelet activation and causing vasodilation. Aspirin irreversibly inhibits COX-1 in both cells but platelets (anucleate) cannot regenerate COX-1, while endothelium regenerates within hours.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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