Studies on receptor binding and signal transduction pathways of unoprostone isopropyl

We examined the binding characteristics of unoprostone isopropyl and its me tabolite, M-1 (M-1), in bovine corpus luteum membranes, mobilization of int racellular calcium in human ciliary muscle cells and cyclic AMP generation in rabbit iris-ciliary body. The ligand binding assay of H-3-unoprostone is opropyl and M-1 did not demonstrate any specific binding of these compounds in the bovine corpus luteum membranes. However, there was a high specific binding of prostaglandin F-2 alpha. Competitive ligand binding studies show ed that neither the docosanoid, unoprostone isopropyl, nor M-1 binds to pro staglandin receptor sites. In human ciliary muscle cells that express EP1, EP2 and FP receptors, unoprostone isopropyl did not increase the mobilizati on of intracellular calcium nor was it able to generate cyclic AMP at low c oncentrations in rabbit iris-ciliary body. Similar observations were made w ith M-1 on the above signal transduction pathways. From these results, it i s concluded that unoprostone isopropyl and M-1 do not bind to prostaglandin (PG) receptor sites in the bovine corpus luteum membranes and do not have affinity for PG receptors linked to intracellular calcium and cyclic AMP se cond messenger systems.