Fig 3. 19(S)-HETE is an orthosteric prostacyclin receptor agonist.

(A) Effect of increasing concentrations of PGI₂, 19(S)-HETE and 19(R)-HETE on cAMP levels in COS-1 transfected with IP receptor and an intracellular cAMP-sensitive bioluminescent probe (see Material and Methods). (B) Effect of different HETEs at 1 μM and of cicaprost (1 μM) on cAMP levels in COS-1 expressing IP receptor and the intracellular bioluminescent cAMP probe. (C) Effect of COX-1/2 blockers indomethacin (10 μM), NS-398 (10 μM) and FR122047 (1 μM) on formation of cAMP induced by 19(S)-HETE (1 μM), arachidonic acid (3 mM), cicaprost (1 μM) and forskolin (10 μM) in COS-1 cells expressing IP receptor. (D) Effect of iloprost and 19(S)-HETE on binding of 10 nM [³H]-iloprost to IP receptor expressed in COS-1 cells. Shown are mean values ± SEM, n ≥ 3. *, P ≤ 0.05; ns, not significant.