Effects of lubiprostone on human uterine smooth muscle cells

Lubiprostone, a bicyclic fatty acid derivative and member of a new class of compounds called prostones, locally activates ClC-2 Cl(-) channels without activation of prostaglandin receptors. The present study was specifically designed to test and compare lubiprostone and prostaglandin effects at the cellular level using human uterine smooth muscle cells. Effects on Ca(2+)](i), membrane potential and cAMP](i) in human uterine smooth muscle cells were measured. 10 nM lubiprostone significantly decreased Ca(2+)](i) from 188 to 27 nM, which was unaffected by 100 nM SC-51322, a prostaglandin EP receptor antagonist. In contrast 10nM PGE(2) and PGE(1) both increased Ca(2+)](i) 3-5-fold which was blocked by SC-51322. Similarly, lubiprostone and prostaglandins had opposite/different effects on membrane potential and cAMP](i). Lubiprostone caused SC-51322-insensitive membrane hyperpolarization and no effect on cAMP](i). PGE(2) and PGE(1) both caused SC-51322-sensitive membrane depolarization and increased cAMP](i). Lubiprostone has fundamentally different cellular effects from prostaglandins that are not mediated by EP receptors.