Endogenous prostaglandin formation in the field-stimulated guinea pig vas deferens: comparison of the inhibitory effects of indomethacin and NS-398

Prostaglandin (PG) E-2 inhibited both phases of contraction produced by ele ctrical field stimulation of the guinea-pig vas deferens. PGF(2 alpha) and PGD(2) were without effect on this preparation. Carbacyclin (a PGI(2)) anal ogue inhibited the first phase of contraction at higher concentrations, whe reas U46619 (a thromboxane mimetic) potentiated both phases of contraction. As exogenous arachidonic acid inhibits both phases of contraction of the e lectrically field-stimulated guinea-pig vas deferens, it is likely that the arachidonic acid is converted to PGE(2) in the vas deferens. Indomethacin, a non-specific inhibitor of prostaglandin H synthase (PGHS), attenuated th e inhibitory actions of exogenous arachidonic acid when examined on the fir st phase of contraction. NS-398, a relatively specific inhibitor of PGHS-2, also prevented the inhibitory action of exogenous arachidonic acid. Howeve r, NS-398 was much less effective than indomethacin in this respect even th ough NS-398 and indomethacin inhibit PGHS-2 with similar potencies. Consequ ently, the findings suggest that exogenous arachidonic acid is converted to PGE(2) in the guinea-pig vas deferens by the actions of PGHS-1 and, to a l esser extent, by PGHS-2. (C) 1999 Harcourt Publishers Ltd.