Stimulation of phosphate transport in the proximal tubule by metabolic substrates

Studies of phosphate transport in the proximal tubule have recently focused on interactions with cellular metabolism. The present studies demonstrate that two fatty acids, valerate and butyrate, and two tricarboxylic acid cycle intermediates, succinate and malate, stimulate net phosphate transport in the rabbit proximal tubule by 34-117%. Valerate had no effect on the total uptake of inorganic [32P]phosphate into suspensions of proximal tubules but did enhance the initial rate of influx. Net fluid transport was unaffected by these substrates although glucose absorption increased by 10-15% following the addition of either valerate or succinate. Since valerate, butyrate, and succinate are known to stimulate gluconeogenesis and respiration, we evaluated the role of gluconeogenesis in the stimulation of phosphate transport. The addition of 3-mercaptopicolinate (1 mM), an inhibitor of gluconeogenesis, did not alter phosphate transport, nor did it prevent the valerate-induced stimulation of phosphate transport. We conclude that valerate, butyrate, succinate, and malate enhance phosphate transport by the proximal convoluted tubule. This action appears to be unrelated to effects on gluconeogenesis and may be related to close links between phosphate transport and oxidative metabolism.