Thromboxane and Stable Prostaglandin Endoperoxide Analogs Stimulate Water Permeability in the Toad Urinary Bladder

Ronald M. Burch; Perry V. Halushka

doi:10.1172/JCI109976

Thromboxane and Stable Prostaglandin Endoperoxide Analogs Stimulate Water Permeability in the Toad Urinary Bladder

Ronald M. Burch and Perry V. Halushka

Published December 1, 1980 - More info

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Abstract

The effects of thromboxane B₂ and the stable prostaglandin endoperoxide analogs (15Z)-hydroxy - 9α - 11α - (epoxymethano)prosta - 5Z,13E - dienoic acid (U44069) and (15Z)-hydroxy -11α,9α-(epoxymethano) prosta-5Z,13E-dienoic acid (U46619) were tested on water flow across the toad urinary bladder. In the presence of indomethacin or meclofenamic acid, inhibitors of prostaglandin and thromboxane A₂ synthesis, thromboxane B₂ stimulated water flow in a dose-dependent manner. U44069 (1 μM) stimulated water flow from 3.6±0.8 to 12.4±1.2 mg/min per 10 cm² hemibladder surface area, while U46619 (1 μM) stimulated water flow from 2.8±1.0 to 21.8±2.0 mg/min per 10 cm². The prostaglandin endoperoxide/thromboxane A₂ antagonist trans- 13-azaprostanoic acid, an inhibitor of vasopressin-stimulated water flow, inhibited thromboxane B₂- and U46619-stimulated water flow in a dose-dependent manner. The inactive cis-13-azaprostanoic acid did not inhibit vasopressin-stimulated water flow in untreated hemibladders and had no effect on U46619-stimulated water flow in indomethacin or meclofenamic acid pretreated hemibladders. U46619 (1 μM) enhanced vasopressin-stimulated water flow in indomethacin pretreated hemibladders, producing a significant parallel shift (P < 0.001) in the dose-response relationship to submaximal concentrations of vasopressin (0.1-0.6 mU/ml), while not affecting water flow stimulated by supramaximal concentrations of vasopressin (10 mU/ml). trans-13-Azaprostanoic acid abolished the potentiating effects of U46619 on vasopressin-stimulated water flow. These results show that thromboxane A₂-like compounds stimulate water flow in the toad urinary bladder.