Effect of prostaglandin E1 on the permeability response of the isolated collecting tubule to vasopressin, adenosine 3′,5′-monophosphate, and theophylline

Abstract

The effect of prostaglandin E₁ (PGE₁) on the water permeability response to vasopressin, theophylline, and cyclic adenosine 3′,5′-monophosphate (C-AMP) of isolated, perfused collecting tubules of the rabbit was investigated in vitro. Prostaglandin is a naturally occurring substance present in a number of tissues, including kidney. It has been implicated in the action of a variety of hormones, many of which are known to exert their physiological effects through the intermediacy of the C-AMP system. In the collecting tubule, PGE₁ (10^-7 M) elicited a minimal increase in net water absorption along an osmotic gradient. However, when administered in association with a concentration of vasopressin (2.5 μU ml^-1) selected to induce a submaximal increment in water absorption, the effect of the latter was reduced by approximately 50%. Theophylline (5 × 10^-3 M) also increased net water absorption, an effect not previously demonstrated in renal tissue. This effect was potentiated by the simulataneous addition of PGE₁. In contrast, PGE₁ did not influence the increase in net water absorption induced by C-AMP (10^-2 M). Since C-AMP is responsible for the permeability effects of vasopressin in renal tissue, the present results are consistent with the view that PGE₁ interferes with the action of the octapeptide by competing with it at a site which influences the generation of C-AMP. In addition it is proposed that prostaglandin may be an important modulator of the action of vasopressin. The tubule is exquisitely sensitive to the hormone, responding to as little as 0.25 μU ml^-1. It is conceivable that in the intact animal prostaglandin may serve to dampen the effects of small amounts of residual hormone and thereby prevent overshoots in permeability which might otherwise occur.