Abstract
In a study of the rat intestinal P(i) transport system, an activator protein for rat Na/P(i) co-transport system (PiUS) was isolated and characterized. We also investigated the effects of restriction of vitamin D and P(i) (two of the most important physiological and pathophysiological regulators of P(i) absorption in the small intestine) on intestinal P(i) transport activity and the expression of Na/P(i) co-transporters that are expressed in rat small intestine. Rat PiUS encodes a 424-residue protein with a calculated molecular mass of 51463 Da. The microinjection of rat PiUS into Xenopus oocytes markedly stimulated Na(+)-dependent P(i) co-transport activity. In rats fed with a low-P(i) diet, Na(+)-dependent P(i) co-transport activity was increased approx. 2-fold compared with that of rats fed a normal P(i) diet. Kinetic studies demonstrated that this increased activity was due to an elevation of V(max) but not K(m). The PiUS mRNA levels showed an approximate doubling in the rats fed with the low-P(i) diet compared with those fed with the normal P(i) diet. In addition, after the administration of 1, 25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] to vitamin D-deficient animals, the P(i) uptake was significantly increased in the Na(+)-dependent component in the brush border membrane vesicle (BBMV) at 24 and 48 h. In addition, we found a further high-affinity Na/P(i) co-transport system in the BBMV isolated from the vitamin D-replete animals. The levels of type III Na/P(i) co-transporter PiT-2 mRNA were increased 24 and 48 h after 1,25-(OH)(2)D(3) administration to vitamin D-deficient animals, whereas PiUS and the type IIb Na/P(i) co-transporter mRNA levels were unchanged. In conclusion, we first cloned a rat activator protein, PiUS, and then studied its role along with that of other type III Na/P(i) co-transporters. PiUS and PiT-2 might be important components in the regulation of the intestinal P(i) transport system by P(i) restriction and 1,25-(OH)(2)D(3).
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- Berner W., Kinne R., Murer H. Phosphate transport into brush-border membrane vesicles isolated from rat small intestine. Biochem J. 1976 Dec 15;160(3):467–474. doi: 10.1042/bj1600467. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Biber J., Custer M., Magagnin S., Hayes G., Werner A., Lötscher M., Kaissling B., Murer H. Renal Na/Pi-cotransporters. Kidney Int. 1996 Apr;49(4):981–985. doi: 10.1038/ki.1996.139. [DOI] [PubMed] [Google Scholar]
- Borowitz S. M., Ghishan F. K. Maturation of jejunal phosphate transport by rat brush border membrane vesicles. Pediatr Res. 1985 Dec;19(12):1308–1312. doi: 10.1203/00006450-198512000-00021. [DOI] [PubMed] [Google Scholar]
- Boyer C. J., Baines A. D., Beaulieu E., Béliveau R. Immunodetection of a type III sodium-dependent phosphate cotransporter in tissues and OK cells. Biochim Biophys Acta. 1998 Jan 5;1368(1):73–83. doi: 10.1016/s0005-2736(97)00159-4. [DOI] [PubMed] [Google Scholar]
- Brandis M., Harmeyer J., Kaune R., Mohrmann M., Murer H., Zimolo Z. Phosphate transport in brush-border membranes from control and rachitic pig kidney and small intestine. J Physiol. 1987 Mar;384:479–490. doi: 10.1113/jphysiol.1987.sp016465. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brautbar N., Levine B. S., Walling M. W., Coburn J. W. Intestinal absorption of calcium: role of dietary phosphate and vitamin D. Am J Physiol. 1981 Jul;241(1):G49–G53. doi: 10.1152/ajpgi.1981.241.1.G49. [DOI] [PubMed] [Google Scholar]
- Cheng L., Sacktor B. Sodium gradient-dependent phosphate transport in renal brush border membrane vesicles. J Biol Chem. 1981 Feb 25;256(4):1556–1564. [PubMed] [Google Scholar]
- Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
- Cross H. S., Debiec H., Peterlik M. Mechanism and regulation of intestinal phosphate absorption. Miner Electrolyte Metab. 1990;16(2-3):115–124. [PubMed] [Google Scholar]
- Cross H. S., Peterlik M. Hormonal regulation of phosphate transport in the differentiating chick small intestine. Adv Exp Med Biol. 1982;151:127–135. doi: 10.1007/978-1-4684-4259-5_18. [DOI] [PubMed] [Google Scholar]
- Custer M., Spindler B., Verrey F., Murer H., Biber J. Identification of a new gene product (diphor-1) regulated by dietary phosphate. Am J Physiol. 1997 Nov;273(5 Pt 2):F801–F806. doi: 10.1152/ajprenal.1997.273.5.F801. [DOI] [PubMed] [Google Scholar]
- Danisi G., Bonjour J. P., Straub R. W. Regulation of Na-dependent phosphate influx across the mucosal border of duodenum by 1,25-dihydroxycholecalciferol. Pflugers Arch. 1980 Dec;388(3):227–232. doi: 10.1007/BF00658486. [DOI] [PubMed] [Google Scholar]
- Danisi G., Caverzasio J., Trechsel U., Bonjour J. P., Straub R. W. Phosphate transport adaptation in rat jejunum and plasma level of 1,25-dihydroxyvitamin D3. Scand J Gastroenterol. 1990 Mar;25(3):210–215. [PubMed] [Google Scholar]
- Danisi G., Murer H., Straub R. W. Effect of pH on phosphate transport into intestinal brush-border membrane vesicles. Am J Physiol. 1984 Feb;246(2 Pt 1):G180–G186. doi: 10.1152/ajpgi.1984.246.2.G180. [DOI] [PubMed] [Google Scholar]
- Danisi G., van Os C. H., Straub R. W. Phosphate transport across brush border and basolateral membrane vesicles of small intestine. Prog Clin Biol Res. 1984;168:229–234. [PubMed] [Google Scholar]
- Ferraro C., Ladizesky M., Cabrejas M., Montoreano R., Mautalen C. Intestinal absorption of phosphate: action of protein synthesis inhibitors and glucocorticoids in the rat. J Nutr. 1976 Dec;106(12):1752–1756. doi: 10.1093/jn/106.12.1752. [DOI] [PubMed] [Google Scholar]
- Hildmann B., Storelli C., Danisi G., Murer H. Regulation of Na+-Pi cotransport by 1,25-dihydroxyvitamin D3 in rabbit duodenal brush-border membrane. Am J Physiol. 1982 May;242(5):G533–G539. doi: 10.1152/ajpgi.1982.242.5.G533. [DOI] [PubMed] [Google Scholar]
- Hilfiker H., Hattenhauer O., Traebert M., Forster I., Murer H., Biber J. Characterization of a murine type II sodium-phosphate cotransporter expressed in mammalian small intestine. Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14564–14569. doi: 10.1073/pnas.95.24.14564. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hopfer U., Nelson K., Perrotto J., Isselbacher K. J. Glucose transport in isolated brush border membrane from rat small intestine. J Biol Chem. 1973 Jan 10;248(1):25–32. [PubMed] [Google Scholar]
- Katai K., Segawa H., Haga H., Morita K., Arai H., Tatsumi S., Taketani Y., Miyamoto K., Hisano S., Fukui Y. Acute regulation by dietary phosphate of the sodium-dependent phosphate transporter (NaP(i)-2) in rat kidney. J Biochem. 1997 Jan;121(1):50–55. doi: 10.1093/oxfordjournals.jbchem.a021569. [DOI] [PubMed] [Google Scholar]
- Kavanaugh M. P., Kabat D. Identification and characterization of a widely expressed phosphate transporter/retrovirus receptor family. Kidney Int. 1996 Apr;49(4):959–963. doi: 10.1038/ki.1996.135. [DOI] [PubMed] [Google Scholar]
- Lee D. B., Walling M. W., Brautbar N. Intestinal phosphate absorption: influence of vitamin D and non-vitamin D factors. Am J Physiol. 1986 Mar;250(3 Pt 1):G369–G373. doi: 10.1152/ajpgi.1986.250.3.G369. [DOI] [PubMed] [Google Scholar]
- Levenson R. Isoforms of the Na,K-ATPase: family members in search of function. Rev Physiol Biochem Pharmacol. 1994;123:1–45. doi: 10.1007/BFb0030902. [DOI] [PubMed] [Google Scholar]
- Levi M., Lötscher M., Sorribas V., Custer M., Arar M., Kaissling B., Murer H., Biber J. Cellular mechanisms of acute and chronic adaptation of rat renal P(i) transporter to alterations in dietary P(i). Am J Physiol. 1994 Nov;267(5 Pt 2):F900–F908. doi: 10.1152/ajprenal.1994.267.5.F900. [DOI] [PubMed] [Google Scholar]
- Li H., Xie Z. Molecular cloning of two rat Na+/Pi cotransporters: evidence for differential tissue expression of transcripts. Cell Mol Biol Res. 1995;41(5):451–460. [PubMed] [Google Scholar]
- Liang C. T., Barnes J., Balakir R., Cheng L., Sacktor B. In vitro stimulation of phosphate uptake in isolated chick renal cells by 1,25-dihydroxycholecalciferol. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3532–3536. doi: 10.1073/pnas.79.11.3532. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Loghman-Adham M. Adaptation to changes in dietary phosphorus intake in health and in renal failure. J Lab Clin Med. 1997 Feb;129(2):176–188. doi: 10.1016/s0022-2143(97)90137-2. [DOI] [PubMed] [Google Scholar]
- Minami H., Kim J. R., Tada K., Takahashi F., Miyamoto K., Nakabou Y., Sakai K., Hagihira H. Inhibition of glucose absorption by phlorizin affects intestinal functions in rats. Gastroenterology. 1993 Sep;105(3):692–697. doi: 10.1016/0016-5085(93)90884-f. [DOI] [PubMed] [Google Scholar]
- Miyamoto K., Tatsumi S., Sonoda T., Yamamoto H., Minami H., Taketani Y., Takeda E. Cloning and functional expression of a Na(+)-dependent phosphate co-transporter from human kidney: cDNA cloning and functional expression. Biochem J. 1995 Jan 1;305(Pt 1):81–85. doi: 10.1042/bj3050081. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murer H., Biber J. A molecular view of proximal tubular inorganic phosphate (Pi) reabsorption and of its regulation. Pflugers Arch. 1997 Feb;433(4):379–389. doi: 10.1007/s004240050292. [DOI] [PubMed] [Google Scholar]
- Murer H., Hopfer U., Kinne R. Sodium/proton antiport in brush-border-membrane vesicles isolated from rat small intestine and kidney. Biochem J. 1976 Mar 15;154(3):597–604. [PMC free article] [PubMed] [Google Scholar]
- Nakagawa N., Ghishan F. K. Low phosphate diet upregulates the renal and intestinal sodium-dependent phosphate transporter in vitamin D-resistant hypophosphatemic mice. Proc Soc Exp Biol Med. 1994 Feb;205(2):162–167. doi: 10.3181/00379727-205-43692. [DOI] [PubMed] [Google Scholar]
- Ni B., Rosteck P. R., Jr, Nadi N. S., Paul S. M. Cloning and expression of a cDNA encoding a brain-specific Na(+)-dependent inorganic phosphate cotransporter. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5607–5611. doi: 10.1073/pnas.91.12.5607. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Norbis F., Boll M., Stange G., Markovich D., Verrey F., Biber J., Murer H. Identification of a cDNA/protein leading to an increased Pi-uptake in Xenopus laevis oocytes. J Membr Biol. 1997 Mar 1;156(1):19–24. doi: 10.1007/s002329900183. [DOI] [PubMed] [Google Scholar]
- Peerce B. E. Simultaneous occlusion of Na+ and phosphate by the intestinal brush border membrane Na+/phosphate cotransporter. Kidney Int. 1996 Apr;49(4):988–991. doi: 10.1038/ki.1996.141. [DOI] [PubMed] [Google Scholar]
- Peterlik M., Wasserman R. H. Effect of vitamin D on transepithelial phosphate transport in chick intestine. Am J Physiol. 1978 Apr;234(4):E379–E388. doi: 10.1152/ajpendo.1978.234.4.E379. [DOI] [PubMed] [Google Scholar]
- Peterlik M., Wasserman R. H. Regulation by vitamin D of intestinal phosphate absorption. Horm Metab Res. 1980 May;12(5):216–219. doi: 10.1055/s-2007-996246. [DOI] [PubMed] [Google Scholar]
- Quamme G. A. Phosphate transport in intestinal brush-border membrane vesicles: effect of pH and dietary phosphate. Am J Physiol. 1985 Aug;249(2 Pt 1):G168–G176. doi: 10.1152/ajpgi.1985.249.2.G168. [DOI] [PubMed] [Google Scholar]
- Shirazi-Beechey S. P., Beechey R. B., Penny J., Vayro S., Buchan W., Scott D. Mechanisms of phosphate transport in sheep intestine and parotid gland: response to variation in dietary phosphate supply. Exp Physiol. 1991 Mar;76(2):231–241. doi: 10.1113/expphysiol.1991.sp003489. [DOI] [PubMed] [Google Scholar]
- Taketani Y., Segawa H., Chikamori M., Morita K., Tanaka K., Kido S., Yamamoto H., Iemori Y., Tatsumi S., Tsugawa N. Regulation of type II renal Na+-dependent inorganic phosphate transporters by 1,25-dihydroxyvitamin D3. Identification of a vitamin D-responsive element in the human NAPi-3 gene. J Biol Chem. 1998 Jun 5;273(23):14575–14581. doi: 10.1074/jbc.273.23.14575. [DOI] [PubMed] [Google Scholar]
- Tanaka H., Miyamoto K. I., Morita K., Haga H., Segawa H., Shiraga T., Fujioka A., Kouda T., Taketani Y., Hisano S. Regulation of the PepT1 peptide transporter in the rat small intestine in response to 5-fluorouracil-induced injury. Gastroenterology. 1998 Apr;114(4):714–723. doi: 10.1016/s0016-5085(98)70585-2. [DOI] [PubMed] [Google Scholar]
- Tatsumi S., Segawa H., Morita K., Haga H., Kouda T., Yamamoto H., Inoue Y., Nii T., Katai K., Taketani Y. Molecular cloning and hormonal regulation of PiT-1, a sodium-dependent phosphate cotransporter from rat parathyroid glands. Endocrinology. 1998 Apr;139(4):1692–1699. doi: 10.1210/endo.139.4.5925. [DOI] [PubMed] [Google Scholar]
- Walling M. W. Intestinal Ca and phosphate transport: differential responses to vitamin D3 metabolites. Am J Physiol. 1977 Dec;233(6):E488–E494. doi: 10.1152/ajpendo.1977.233.6.E488. [DOI] [PubMed] [Google Scholar]
- Wasserman R. H., Taylor A. N. Intestinal absorption of phosphate in the chick: effect of vitamin D and other parameters. J Nutr. 1973 Apr;103(4):586–599. doi: 10.1093/jn/103.4.586. [DOI] [PubMed] [Google Scholar]
- Welch R. W., Bergsten P., Butler J. D., Levine M. Ascorbic acid accumulation and transport in human fibroblasts. Biochem J. 1993 Sep 1;294(Pt 2):505–510. doi: 10.1042/bj2940505. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yagci A., Werner A., Murer H., Biber J. Effect of rabbit duodenal mRNA on phosphate transport in Xenopus laevis oocytes: dependence on 1,25-dihydroxy-vitamin-D3. Pflugers Arch. 1992 Dec;422(3):211–216. doi: 10.1007/BF00376204. [DOI] [PubMed] [Google Scholar]