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Abstract #6834 Published in IGR 4-1
Comparison between isopropyl unoprostone and latanoprost by prostaglandin E2 induction, affinity to prostaglandin transporter, and intraocular metabolism
Kashiwagi K; Kanai N; Tsuchida T; Suzuki M; Iizuka Y; Tanaka Y; Tsukahara SExperimental Eye Research 2002; 74: 41-49
The pharmacological differences between isopropyl unoprostone (referred to as unoprostone) and latanoprost, with regard to 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 PGF2α, and PGE2 induction was measured. Affinities of M1, M2, latanoprost, acid of latanoprost, and PGF2α 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 of 3H-unoprostone M2, acid of latanoprost, and PGF2α significantly increased a release of PGE2 compared with the control. Ten μm indomethacin completely inhibited PGE2 induction by acid of latanoprost and PGF2α, while 100 μm indomethacin was required to inhibit PGE2 induction 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 PGE2 may play an important role of action by means of PG analogues, and differences in indomethacin-related inhibition of PGE2 release and in affinities to PGT may in part cause their different actions.
Dr. K. Kashiwagi, Department of Ophthalmology, Yamanashi Medical University, Japan. kenjik@res.yamanashi-med.ac.jp
Classification:
11.4 Prostaglandins (Part of: 11 Medical treatment)
