Relationship among parathyroid hormone, cAMP, and calcium on proximal tubule sodium transport

Abstract

Parathyroid hormone (PTH), through the generation of cAMP, inhibits the transport of sodium, bicarbonate, and water in the proximal convoluted tubule. The present studies were designed to determine whether the response to PTH or dibutyryl cAMP by proximal renal tubules requires an influx of calcium into the cells or an alteration in the cytosolic concentration of calcium. O2 consumption was determined in an enriched suspension of rabbit proximal convoluted tubules, and the ouabain-sensitive component of O2 consumption was taken as a measure of sodium transport. PTH (1 IU/ml) inhibited the ouabain-sensitive component of O2 consumption from 14.2 +/- 1.6 to 8.9 +/- 1.1 nmol O2 X min-1 X mg protein-1 (P less than 0.005). Dibutyryl cAMP (10(-4) M) inhibited ouabain-sensitive O2 consumption from 12.0 +/- 1.1 to 8.4 +/- 0.8 nmol O2 X min-1 X mg protein-1 (P less than 0.005). In the presence of lanthanum (5-50 microM) or verapamil (20-200 microM), PTH inhibited ouabain-sensitive O2 consumption by 21.3 +/- 3.4% (P less than 0.025) and 33.9 +/- 5.5% (P less than 0.025), respectively. Dibutyryl cAMP inhibited the ouabain-sensitive O2 consumption by 22.6 +/- 7.1% (P less than 0.025) in the presence of lanthanum and 35.4 +/- 3.1% (P less than 0.01) in the presence of verapamil. To more directly assess the cytosolic concentration of calcium, the fluorescent intensity of quin 2-loaded tubules was determined. As compared with timed controls, exposure to PTH resulted in a lower cytosolic concentration of calcium over the 10 min of incubation. Dibutyryl cAMP had a similar effect.(ABSTRACT TRUNCATED AT 250 WORDS)