Effect of parathyroid hormone and cyclic adenosine 3',5'-monophosphate on isotonic fluid reabsorption: polarity of proximal tubular cells.

Isotomic fluid reabsorption (JV) of rat renal proximal tubules was examined by the shrinking droplet method in combination with simulatneous perfusion of blood capillaries. Sensitivity of JV measurement was improved by using each punctured tubule for control measurements: 1) Parathyroid hormoen (PTH) on the contraluminal cell side reduced JV in a dose-response behavior. The maximal inhibition was achieved at a PTH concentration of 10(-5) M, the half maximal inhibition at a concentration of 3 X 10(-9) M. PTH on the luminal cell side had a small inhibitory effect. 2) Cyclic AMP inhibited JV preferentially when applied to the luminal cell side. On the luminal cell side, both cyclic AMP and dibutyryl cyclic AMP inhibited JV in a similar dose-dependent behavior. Concentrations of both nucleotides as low as 10(-10) M had a definite inhibitory effect. Tested at a high concentration, N6-butyryl cyclic AMP was almost as effective as cyclic AMP. Deoxy cyclic AMP, 5' AMP, cyclic guanosine monophosphate (cyclic GMP), dibutyryl cyclic GMP had no effect. ATP inhibited JV to a very small extent. 3) The reduction of JV after administration of PTH and dibutyryl cyclic AMP was not additive. The similar inhibitory effect of PTH at the contraluminal cell face and of cyclic AMP at the luminal cell face suggests the following sequence of events in the mediation of the action of PTH: 1) activation of adenylate cyclase by PTH in the contraluminal cell membrane, and 2) action of the generated cyclic AMP on the luminal cell membrane. The interaction of cyclic AMP and the luminal cell membrane is initiated at the luminal cell surface.