Inhibition of ADH-stimulated water flow by stable prostaglandin endoperoxide analogues

The synthetic prostaglandin endoperoxide analogues 15-hydroxy-9,11-(epoxymethano)prosta-5,13-dien-1-oic acid (EPA-I) and 15-hydroxy-11,9-(epoxymethano)prosta-5,13-dien-1-oic acid (EPA-II) inhibited ADH-induced water flow in the isolated urinary bladder of the toad. In certain other biologic systems, EPA-I appeared to possess "thromboxane-like" activity. Thromboxanes, therefore, as well as the classical E prostaglandins may be modulators of the ADH response. To further characterize the effect of EPA-I on ADH, interaction studies were conducted with a related endoperoxide analogue found to be devoid of anti-ADH activity, 9,11-(epoxymethano)prostan-1-oic acid (EPA-III), and a prostanoid found to be a PGE antagonist in isolated toad bladder, 7-oxa-13-prostynoic acid. EPA-III reversed the anti-ADH activity of EPA-I but not that of PGE2. In contrast, 7-oxa-13-prostynoic acid reversed the anti-ADH activity of PGE2 but not that of an equieffective concentration of EPA-I. These findings suggest that the anti-ADH activity of EPA-I, and by inference thromboxane A2, may be mediated via a different receptor and/or pathway than that of the E prostaglandins.