Angiotensin and prostaglandin interactions in cultured kidney tubules.

Angiotensin and prostaglandin interactions in cultured kidney tubules were studied in tissue from fetal calves. Methods were developed for the isolation and culture of renal proximal tubule cells. Tubule cells survived three generations in culture. They had microvilli and flagellae characteristic of proximal tubule cells. Binding of 125I-angiotensin II to receptor-like sites in cells and homogenates was partially saturable, and the saturable binding was reversed by excess unlabeled hormone. Two types of binding sites were identified by Scatchard analysis. The higher-affinity site had a dissociation constant of 5 X 10(-10)M. PGE2 and PGA2 inhibited angiotensin binding. PGF2 alpha had no effect. Cultured tubule cells were loaded with 22Na+ by incubation in hypoxic medium free of potassium and glucose. Cells extruded the sodium when oxygen, glucose, and potassium were added. The rate of extrusion was accelerated by angiotensin II at concentrations of 10(-10)M and 10(-9)M. Higher concentrations had less effect. The primary prostaglandins PGA2 and PGF2 alpha inhibited 22Na+ efflux at 6 X 10(-7)M. Angiotensin had no detectable effect on sodium efflux in the presence of PGA2. Angiotensin apparently reversed inhibition of efflux by PGF2 alpha. Our findings suggest that prostaglandins affect angiotensin receptors in renal tubule cells. Prostaglandins also have direct effects on sodium efflux in these cells under the experimental conditions described.