Comparison between Isopropyl Unoprostone and Latanoprost by Prostaglandin E2Induction, Affinity to Prostaglandin Transporter, and Intraocular Metabolism

Abstract

The pharmacological differences between isopropyl unoprostone (referred to as unoprostone) and latanoprost, concerning their induction of endogenous prostaglandin E2(PGE2) and affinity to a human prostaglandin transporter (PGT), were investigated.Freshly dissected bovine iris tissues were incubated with major intraocular metabolites of unoprostone, M1 and M2, acid of latanoprost, or PGF2 α, and PGE2induction was measured. Affinities of M1, M2, latanoprost, acid of latanoprost, and PGF2αto PGT molecule were measured using PGT-cDNA transfected HeLa cells by an isotopic influx assay.3H-unoprostone was incubated with freshly prepared serum, aqueous humor, or frozen stored fetal bovine serum (FBS), and the radioactivity of supernatants was measured to investigate their metabolism of3H-unoprostone.M2, acid of latanoprost, and PGF2 αsignificantly increased a release of PGE2compared with the control. 10μM indomethacin completely inhibited PGE2induction by acid of latanoprost and PGF2 α, while 100μM indomethacin was required to inhibit PGE2induction completely by M1 and M2. Unoprostone, M1, M2, and latanoprost showed little affinity to PGT, while acid of latanoprost had an affinity to PGT. Freshly prepared serum and aqueous humor metabolized unoprostone, but frozen stored FBS did not. The release of endogenous PGE2may play an important role of action by means of PG analogs, and differences in indomethacin-related inhibition of PGE2release and in affinities to PGT may in part cause their different actions.