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

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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 .cntdot. min-1 .cntdot. mg protein-1 (P < 0.005). Dibutyryl cAMP (10-4 M) inhibited ouabain-sensitive O2 consumption from 12.0 .+-. 1.1 to 8.4 .+-. 0.8 nmol O2 .cntdot. min-1 .cntdot. mg protein-1 (P < 0.005). In the presence of lanthanum (5-50 .mu.M) or verapamil (20-200 .mu.M), PTH inhibited ouabain-sensitive O2 consumption by 21.3 .+-. 3.4% (P < 0.025) and 33.9 .+-. 5.5% (P < 0.025), respectively. Dibutyryl cAMP inhibited the ouabain-sensitive O2 consumption by 22.6 .+-. 7.1% (P < 0.025) in the presence of lanthanum and 35.4 .+-. 3.1% (P < 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. These studies indicated that an influx of calcium from the bath into the cells is not required for PTH or dibutyryl cAMP to inhibit sodium transport in proximal convoluted tubules of the rabbit. Moreover, as determined by quin 2 fluorescence measurements, exposure of rabbit proximal tubules to PTH or dibutyryl cAMP is associated with a significant decrease rather than an increase in the cytosolic concentration of calcium.