The authors explored whether glucocorticoid administration, a known stimulus of renal gluconeogenesis (GNG), could decrease avid inorganic phosphate [P(i)] reabsorption in rats stabilized on low-phosphorus diet (LPD). Rats adapted to LPD were injected with the glucocorticoid (GCD) triamcinolone acetonide (1.25 or 2.5 mg.100 g body wt-1.day-1 ip) for 2 days; they showed a profound increase in urinary excretion of P(i) during the injection period. In clearance studies GCD increased the clearance and fractional excretion of P(i) but did not change the filtered load of P(i). Initial 'uphill' Na+-gradient [Na(o)+ > Na(i)+]-dependent uptake of 32P(i) by luminal brush-border membrane (BBM) vesicles prepared from renal cortex of rats treated with GCD was markedly (> 40%) decreased compared with control rats; Na+-gradient-dependent uptake of D-[3H]glucose was not diminished. At the 'equilibrium' time interval, measured at 120 min, BBM vesicles from control and GCD-treated rats did not differ in the uptake of 32P(i) or D-[3H]glucose. With kinetic analysis, BBM from GCD-treated rats showed a marked decrease (-40%) in the maximum velocity [V(max)] of initial Na+-dependent 32P(i) uptake, but the apparent affinity of the BBM transport system for P(i) [apparent K(m) = 0.078 mM P(i)] was not different from that of controls. Alkaline phosphatase specific activity was much lower (-40%) in BBM from GCD-treated rats compared with controls, but the activities of three other BBM enzymes (maltase, leucine aminopeptidase, and γ-glutamyl transferase) were not different. The addition of triamcinolone to BBM in vitro had no effect on either Na+-dependent uptake of 32P(i) or alkaline phosphatase activity. The rate of GNG from α-ketoglutarate was significantly increased in cortical slices from GCD-treated rats adapted to LPD. Also, the NAD+-to-NADH ratio was higher in the renal cortex of GCD-treated rats, although the total content of NAD [NAD+ + NADH] was not different from controls. Renal excretory, BBM, and metabolic changes elicited by GCD treatment were similar in intact and thyroparathyroidectomized rats. Phosphaturia elicited in rats fed LPD by GCD administration in vivo appears to be at least in part due to a decreased capacity of luminal BBM of proximal tubules for Na+-dependent uptake of P(i). Although the causal relationship between observed parameters is not established, the results are compatible with the interpretation that an increase in the rate of renal GNG, perhaps via action of NAD+ on BBM, decreases luminal uptake and reabsorption of P(i) in proximal tubules.
ASJC Scopus subject areas
- Cell Biology