Background:

Trequinsin is a phosphodiesterase (PDE) 3 inhibitor that is dependent on cyclic AMP (cAMP), with IC50 values of 0.04 and 0.03 nM for PDE3A and PDE3B, respectively, in T84 human colonic adenocarcinoma cell lysates.[1] In cultured primary rat juxtaglomerular cells, trequinsin stimulates cAMP accumulation when used at a concentration of 10 μM and increases cell membrane capacitance in a patch clamp assay.[2] Trequinsin also competitively inhibits the multidrug resistant protein 5-mediated export of cGMP from Chinese hamster lung fibroblasts with a Ki value of 240 nM.[3] In vivo, trequinsin reduces collagen-induced platelet aggregation in rabbits when administered intravenously at a rate of 3 μg/kg per minute, as well as the collagen-induced decrease in mean arterial blood pressure when administered alone or in combination with prostacyclin.[4]

Reference:
[1]. Liu, S., Veilleux, A., Zhang, L., et al. Dynamic activation of cystic fibrosis transmembrane conductance regulator by type 3 and type 4D phosphodiesterase inhibitors. J. Pharmacol. Exp. Ther. 314(2), 846-854 (2005).
[2]. Friis, U.G., Jensen, B.L., Sethi, S., et al. Control of renin secretion from rat juxtaglomerular cells by cAMP-specific phosphodiesterases. Circ. Res. 90(9), 996-1003 (2002).
[3]. Jedlitschky, G., Burchell, B., and Keppler, D. The multidrug resistance protein 5 functions as an ATP-dependent export pump for cyclic nucleotides. J. Biol. Chem. 275(39), 30069-30074 (2000).
[4]. Darius, H., Lefer, A.M., Leprán, I., et al. In vivo interaction of prostacyclin with an inhibitor of cyclic nucleotide phosphodiesterase, HL 725. Br. J. Pharmacol. 84(3), 735-741 (1985).