MOLECULAR-CLONING AND HORMONAL-REGULATION OF PIT-1, A SODIUM-DEPENDENT PHOSPHATE COTRANSPORTER FROM RAT PARATHYROID-GLANDS

The extracellular concentration of inorganic phosphate (P-i) is an imp ortant determinant of parathyroid cell function. The effects of P-i ma y be mediated through specific molecules in the parathyroid cell membr ane, one candidate molecule for which would be a Na+-dependent P-i cot ransporter. A complementary DNA encoding a Na+-P-i cotransporter terme d rat PiT-1, has now been isolated from rat parathyroid. The 2890-bp c omplementary DNA encodes a protein of 681 amino acids that shows seque nce identities of 97% and 93% with the type III Na+-P-i cotransporters mouse PiT-1 and human PiT-1, respectively. Expression of rat PiT-1 in Xenopus oocytes revealed that it possesses Na+-dependent P-i cotransp ort activity. PiT-1 messenger RNA (mRNA) is widely distributed in rat tissues and is most abundant in brain, bone, and small intestine. The amount of PiT-1 mRNA in the parathyroid of vitamin D-deficent rats was reduced compared with that in normal animals and increased markedly a fter administration of 1,25-dihydroxyvitamin D-3. Furthermore, the abu ndance of PiT-1 mRNA in the parathyroid was much greater in rats fed a low-P-i diet than in those fed a high-P-i diet. Thus, rat PiT-1 may c ontribute to the effects of P-i and vitamin D on parathyroid function.