Endogenous prostaglandins and osmotic water flow in the toad bladder.

FLORES, AURA G. A., AND GEOFFREY Mr. G. SHARP. Endogenous prostaglandins and osmotic waterflow in the toad bladder. Am. J. Physiol. 223 (6) : 1392-1397. 1972.-Prostaglandins, at low concentrations, inhibit the osmotic water-flow response to antidiuretic hormone (ADH) and to theophylline in toad bladder. They have no effect upon the response to dibutyryl cyclic AMP. Thus the prustaglandins inhibit adenyl cyclase in this tissue and decrease the stimulation of adenyl cyclase by ADH. It is not known, however, whether endogenous prostaglandins have any physiological role in reducing basal adenyl cyclase activity and hormone responses. As indomethacin inhibits prostaglandin synthetase and thus blocks prostaglandin synthesis and release, it has been used to assess the physiological role of prostaglandins. Indomethacin enhanced the osmotic water-flow response to submaximal concentrations of antidiurelic hcrmone and to dibutyryl cyclic AMP. The effect on the latter was ascribed to the inhibitory effect of indomethacin on phosphodiesterase. On a molar basis, indomethacin was estimated to be more than lo-fold more effective than theophylline in its ability to inhibit phosphodiesterase. Thus potentiation cf the response to ADH by indomethacin, even at low concentrations, is not by itself an indication that endogenous release of prostaglandins exerts a continual restraining influence on adenyl cyclase. However, it was found that indomethacin potentiated the response to high concentrations of theophylline (which alone inhibit phosphodiesterase activity). This effect is ascribed to the lifting of prostaglandin inhibition of adenyl cyclase and indicates that endogenous prostaglandins could have a regulatory role to play in the normal cell function.