Inhibition of renal brush border phosphate transport and stimulation of renal gluconeogenesis by cyclic AMP and parathyroid hormone

Abstract

The aims of the study were to determine whether 8-bromo-cyclic AMP (8BcAMP) in vivo mimics the inhibitory action of parathyroid hormone (PTH) on phosphate transport across the brush border membrane (BBM) of the renal proximal tubule, and to examine whether changes in BBM transport are accompanied by changes in the rate of renal gluconeogenesis. Thyroparathyroidectomized dogs were anesthetized and equilibrated, and control urine collections were obtained prior to removing the left kidney. Subsequent intravenous infusion of 8BcAMP at 50 mg/hr for 2 hr increased fractional excretion of phosphate from 4 ± 1 (controls) to 29 ± 4% (P < 0.001) without changing glomerular filtration. In BBM vesicles isolated from the renal cortex, the initial Na −-dependent transport of phosphate was decreased from 747 ± 135 (controls) to 564 ± 126 pmoles per mg per 0.25 min after 8BcAMP (P < 0.025), but Na −-independent phosphate uptake and Na −-dependent L-proline uptake were not changed significantly. Renal gluconeogenesis in the same animals was increased from 2.5 ± 0.3 (controls) to 5.3 ± 0.5 μmoles glucose per g tissue per hr after infusion of 8BcAMP (P < 0.001). Infusion of PTH, like 8BcAMP, inhibited BBM phosphate transport and stimulated renal gluconeogenesis. We conclude that the inhibitory action of cyclic AMP and PTH on BBM phosphate transport is accompanied by stimulation of gluconeogenesis which suggests, indirectly, that changes in gluconeogenesis may be part of the intracellular mechanism for regulating BBM phosphate uptake in response to certain stimuli.