Altered response of adenylate cyclase to parathyroid hormone during compensatory renal growth

The loss of renal mass is associated with functional adaptations in the remaining nephrons to maintain homeostasis. Although parathyroid hormone (PTH) is important in the adaptations to phosphate, the mechanisms are not completely defined. In the present studies we examined the response of the adenylate cyclase system to PTH in renal cortical membranes of rat kidneys ten days after unilateral nephrectomy. The kidneys obtained at the time of the initial nephrectomy were used as controls. Unilateral nephrectomy resulted in contralateral compensatory renal growth, as demonstrated by a 24 +/- 4.7% (P less than 0.01) increase in weight in the remaining kidney. Glomerular filtration rate (GFR) after unilateral nephrectomy was 62% of the control, while basal fractional phosphate excretion was higher in rats with unilateral nephrectomy (7.7 +/- 2.1% vs. 2.9 +/- 0.8%, P less than 0.05). PTH infusion resulted in a similar increase of fractional phosphate excretion and urinary cAMP in both groups. In the absence of added guanine nucleotides, PTH-dependent adenylate cyclase activity in cortical membranes from kidneys with compensatory growth was decreased as compared to controls (Vmax 807.5 +/- 62.7 pmol cAMP/mg protein/30 min vs. 1,384.8 +/- 116.1, respectively, P less than 0.01). The apparent affinity for PTH stimulation of adenylate cyclase (Kact) was unchanged. Magnesium-dependent adenylate cyclase activity was also decreased in the membranes from kidneys with compensatory growth. However, the kinetics of adenylate cyclase for the substrates ATP-Mg or ATP-Mn were similar.(ABSTRACT TRUNCATED AT 250 WORDS)