Parathyroid hormone inhibition of phosphate transport in renal brush border vesicles from phosphate-depleted dogs

Abstract

Dietary phosphate (P i) restriction increases renal P i reabsorption and induces resistance to the phosphaturic action of parathyroid hormone. Na +-gradient-stimulated P i transport in membrane vesicles isolated from the renal brush border of experimental animals has been shown to parallel changes in renal P i reabsorption induced by dietary P i restriction and in vivo administration of parathyroid hormone. Dietary P i restriction has been shown to markedly inhibit the phosphaturic response to parathyroid hormone in rats and dogs. Parathyroid hormone has been reported not to decrease the Na +-gradient-stimulated transport of P i in brush border membrane vesicles isolated from dietary P i restricted rats unless the rats were administered an acute P i load prior to killing, however, thyroparathyroidectomy of rats fed a low P i diet has been reported to increase Na +-gradient-stimulated P i transport. Using the dietary P i restricted dog, we demonstrated no significant decrease in renal reabsorption of P i in response to parathyroid hormone administration. However, significant decreases in P i transport in brush border membrane vesicles isolated from the kidneys of dietary P i restricted dogs were observed in response to in vivo parathyroid hormone administration. These data demonstrate that the resistance to the phosphaturic action of parathyroid hormone observed in vivo does not include resistance to the inhibitory effect of parathyroid hormone on P i transport in brush border membrane vesicles. Thus, the data suggest that parathyroid hormone continues to alter P i transport characteristics of the brush border membrane in states of P i depletion despite the resistance to parathyroid hormone seen in vivo.