Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1996 Sep 1;98(5):1142–1149. doi: 10.1172/JCI118897

Cloning, in vitro expression, and tissue distribution of a human prostaglandin transporter cDNA(hPGT).

R Lu 1, N Kanai 1, Y Bao 1, V L Schuster 1
PMCID: PMC507536  PMID: 8787677

Abstract

We recently identified a cDNA in the rat that encodes a broadly expressed PG transporter (PGT). Because PGs play diverse and important roles in human health and disease, we cloned human PGT (hPGT) from an adult human kidney cDNA library. A consensus sequence (4.0 kb) derived from several clones, plus 3' polymerase chain reaction amplification, exhibited 74% nucleic acid identity and 82% amino acid identity compared to rat PGT. When transiently expressed in HeLa cells, a full-length clone catalyzed the transport of PGE1, PGE2, PGD2, PGF2alpha, and, to a lesser degree, TXB2. Northern blotting revealed mRNA transcripts of many different sizes in adult human heart, placenta, brain, lung, liver, skeletal muscle, pancreas, kidney, spleen, prostate, ovary, small intestine, and colon. hPGT mRNAs are also strongly expressed in human fetal brain, lung, liver, and kidney. The broad tissue distribution and substrate profile of hPGT suggest a role in the transport and/or metabolic clearance of PGs in diverse human tissues.

Full Text

The Full Text of this article is available as a PDF (364.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alm A., Villumsen J., Törnquist P., Mandahl A., Airaksinen J., Tuulonen A., Marsk A., Resul B., Stjernschantz J. Intraocular pressure-reducing effect of PhXA41 in patients with increased eye pressure. A one-month study. Ophthalmology. 1993 Sep;100(9):1312–1317. doi: 10.1016/s0161-6420(93)31482-x. [DOI] [PubMed] [Google Scholar]
  2. Anderson M. W., Eling T. E. Prostaglandin removal and metabolism by isolated perfused rat lung. Prostaglandins. 1976 Apr;11(4):645–677. doi: 10.1016/0090-6980(76)90067-8. [DOI] [PubMed] [Google Scholar]
  3. Bardhan K. D., Walker R., Hinchliffe R. F., Bose K., Morris P., Thompson M., Miller J. P., Toivanen E., Thompson R. P., Patrier P. Gastric ulcer healing: a comparison of enprostil versus ranitidine. J Clin Gastroenterol. 1991 Apr;13(2):157–162. [PubMed] [Google Scholar]
  4. Bikhazi A. B., Baasiri G. M., Boulos N. Z., Khuri R. N. Transport of prostaglandins through normal and diabetic rat hepatocytes. J Pharm Sci. 1983 Mar;72(3):296–299. doi: 10.1002/jps.2600720322. [DOI] [PubMed] [Google Scholar]
  5. Bito L. Z. Absorptive transport of prostaglandins from intraocular fluids to blood: a review of recent findings. Exp Eye Res. 1973 Aug 10;16(4):299–306. doi: 10.1016/0014-4835(73)90095-x. [DOI] [PubMed] [Google Scholar]
  6. Bito L. Z., Baroody R. A. Impermeability of rabbit erythrocytes to prostaglandins. Am J Physiol. 1975 Dec;229(6):1580–1584. doi: 10.1152/ajplegacy.1975.229.6.1580. [DOI] [PubMed] [Google Scholar]
  7. Bito L. Z., Davson H., Salvador E. V. Inhibition of in vitro concentrative prostaglandin accumulation by prostaglandins, prostaglandin analogues and by some inhibitors of organic anion transport. J Physiol. 1976 Apr;256(2):257–271. doi: 10.1113/jphysiol.1976.sp011324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bito L. Z., Salvador E. V. Effects of anti-inflammatory agents and some other drugs on prostaglandin biotransport. J Pharmacol Exp Ther. 1976 Aug;198(2):481–488. [PubMed] [Google Scholar]
  9. Bito L. Z. Saturable, energy-dependent, transmembrane transport of prostaglandins against concentration gradients. Nature. 1975 Jul 10;256(5513):134–136. doi: 10.1038/256134a0. [DOI] [PubMed] [Google Scholar]
  10. Bito L. Z., Wallenstein M. C. Transport of prostaglandins across the blood-brain and blood-aqueous barriers and the physiological significance of these absorptive transport processes. Exp Eye Res. 1977;25 (Suppl):229–243. doi: 10.1016/s0014-4835(77)80020-1. [DOI] [PubMed] [Google Scholar]
  11. Camras C. B., Schumer R. A., Marsk A., Lustgarten J. S., Serle J. B., Stjernschantz J., Bito L. Z., Podos S. M. Intraocular pressure reduction with PhXA34, a new prostaglandin analogue, in patients with ocular hypertension. Arch Ophthalmol. 1992 Dec;110(12):1733–1738. doi: 10.1001/archopht.1992.01080240073034. [DOI] [PubMed] [Google Scholar]
  12. Cao Z. D., Jones M. A., Harper M. J. Prostaglandin translocation from the lumen of the rabbit uterus in vitro in relation to day of pregnancy or pseudopregnancy. Biol Reprod. 1984 Oct;31(3):505–519. doi: 10.1095/biolreprod31.3.505. [DOI] [PubMed] [Google Scholar]
  13. Cawello W., Schweer H., Müller R., Bonn R., Seyberth H. W. Metabolism and pharmacokinetics of prostaglandin E1 administered by intravenous infusion in human subjects. Eur J Clin Pharmacol. 1994;46(3):275–277. doi: 10.1007/BF00192562. [DOI] [PubMed] [Google Scholar]
  14. Cayeux S. J., Beverley P. C., Schulz R., Dörken B. Elevated plasma prostaglandin E2 levels found in 14 patients undergoing autologous bone marrow or stem cell transplantation. Bone Marrow Transplant. 1993 Dec;12(6):603–608. [PubMed] [Google Scholar]
  15. 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]
  16. DiBenedetto F. E., Bito L. Z. Transport of prostaglandins and other eicosanoids by the choroid plexus: its characterization and physiological significance. J Neurochem. 1986 Jun;46(6):1725–1731. doi: 10.1111/j.1471-4159.1986.tb08490.x. [DOI] [PubMed] [Google Scholar]
  17. Dusting G. J., Moncada S., Vane J. R. Recirculation of prostacyclin (PGI2) in the dog. Br J Pharmacol. 1978 Oct;64(2):315–320. doi: 10.1111/j.1476-5381.1978.tb17307.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Eling T. E., Anderson M. W. Studies on the biosynthesis, metabolism and transport of prostaglandins by the lung. Agents Actions. 1976 Jul;6(4):543–546. doi: 10.1007/BF01973277. [DOI] [PubMed] [Google Scholar]
  19. Eling T. E., Hawkins H. J., Anderson M. W. Structural requirements for, and the effects of chemicals on, the rat pulmonary inactivation of prostaglandins. Prostaglandins. 1977 Jul;14(1):51–60. doi: 10.1016/0090-6980(77)90156-3. [DOI] [PubMed] [Google Scholar]
  20. Ferreira S. H., Vane J. R. Prostaglandins: their disappearance from and release into the circulation. Nature. 1967 Dec 2;216(5118):868–873. doi: 10.1038/216868a0. [DOI] [PubMed] [Google Scholar]
  21. Fuerst T. R., Niles E. G., Studier F. W., Moss B. Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8122–8126. doi: 10.1073/pnas.83.21.8122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Glance D. G., Elder M. G., Myatt L. Uptake, transfer and metabolism of prostaglandin E2 in the isolated perfused human placental cotyledon. Prostaglandins Leukot Med. 1986 Jan;21(1):1–14. doi: 10.1016/0262-1746(86)90157-5. [DOI] [PubMed] [Google Scholar]
  23. Hagen A. A., Gerber J. N., Sweeley C. C., White R. P., Robertson J. T. Levels and disappearance of prostaglandin F2alpha in cerebral spinal fluid: a clinical and experimental study. Stroke. 1977 Nov-Dec;8(6):672–675. doi: 10.1161/01.str.8.6.672. [DOI] [PubMed] [Google Scholar]
  24. Hawkins H. J., Wilson A. G., Anderson M. W., Eling T. E. Uptake and metabolism of prostaglandins by isolated perfused lung: species comparisons and the role of plasma protein binding. Prostaglandins. 1977 Aug;14(2):251–259. doi: 10.1016/0090-6980(77)90170-8. [DOI] [PubMed] [Google Scholar]
  25. Hayaishi O. Molecular mechanisms of sleep-wake regulation: roles of prostaglandins D2 and E2. FASEB J. 1991 Aug;5(11):2575–2581. [PubMed] [Google Scholar]
  26. Hirsh P. D., Hillis L. D., Campbell W. B., Firth B. G., Willerson J. T. Release of prostaglandins and thromboxane into the coronary circulation in patients with ischemic heart disease. N Engl J Med. 1981 Mar 19;304(12):685–691. doi: 10.1056/NEJM198103193041201. [DOI] [PubMed] [Google Scholar]
  27. Irish J. M., 3rd Secretion of prostaglandin E2 by rabbit proximal tubules. Am J Physiol. 1979 Oct;237(4):F268–F273. doi: 10.1152/ajprenal.1979.237.4.F268. [DOI] [PubMed] [Google Scholar]
  28. Ito S., Narumiya S., Hayaishi O. Prostaglandin D2: a biochemical perspective. Prostaglandins Leukot Essent Fatty Acids. 1989 Sep;37(4):219–234. doi: 10.1016/0952-3278(89)90033-1. [DOI] [PubMed] [Google Scholar]
  29. Jacquemin E., Hagenbuch B., Stieger B., Wolkoff A. W., Meier P. J. Expression cloning of a rat liver Na(+)-independent organic anion transporter. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):133–137. doi: 10.1073/pnas.91.1.133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Jones M. A., Harper M. J. Prostaglandin accumulation by isolated uterine endometrical epithelial cells from six-day pregnant rabbits. Biol Reprod. 1983 Dec;29(5):1201–1209. doi: 10.1095/biolreprod29.5.1201. [DOI] [PubMed] [Google Scholar]
  31. Kanai N., Lu R., Bao Y., Wolkoff A. W., Vore M., Schuster V. L. Estradiol 17 beta-D-glucuronide is a high-affinity substrate for oatp organic anion transporter. Am J Physiol. 1996 Feb;270(2 Pt 2):F326–F331. doi: 10.1152/ajprenal.1996.270.2.F326. [DOI] [PubMed] [Google Scholar]
  32. Kanai N., Lu R., Satriano J. A., Bao Y., Wolkoff A. W., Schuster V. L. Identification and characterization of a prostaglandin transporter. Science. 1995 May 12;268(5212):866–869. doi: 10.1126/science.7754369. [DOI] [PubMed] [Google Scholar]
  33. Karim A., Rozek L. F., Smith M. E., Kowalski K. G. Effects of food and antacid on oral absorption of misoprostol, a synthetic prostaglandin E1 analog. J Clin Pharmacol. 1989 May;29(5):439–443. doi: 10.1002/j.1552-4604.1989.tb03358.x. [DOI] [PubMed] [Google Scholar]
  34. Kobayashi K., Arakawa T., Higuchi K., Nakamura H. Gastric cytoprotection by ornoprostil, a PGE1 analogue, in human subjects. J Clin Gastroenterol. 1991;13 (Suppl 1):S32–S36. doi: 10.1097/00004836-199112001-00005. [DOI] [PubMed] [Google Scholar]
  35. Konturek S. J., Kwiecien N., Obtulowicz W., Maczka J., Hebzda Z., Oleksy J. Effects of nocloprost on gastric functions in man. Scand J Gastroenterol. 1991 Nov;26(11):1145–1151. doi: 10.3109/00365529108998606. [DOI] [PubMed] [Google Scholar]
  36. Kozak M. An analysis of vertebrate mRNA sequences: intimations of translational control. J Cell Biol. 1991 Nov;115(4):887–903. doi: 10.1083/jcb.115.4.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  38. Matsumura H., Nakajima T., Osaka T., Satoh S., Kawase K., Kubo E., Kantha S. S., Kasahara K., Hayaishi O. Prostaglandin D2-sensitive, sleep-promoting zone defined in the ventral surface of the rostral basal forebrain. Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):11998–12002. doi: 10.1073/pnas.91.25.11998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Matsumura K., Watanabe Y., Imai-Matsumura K., Connolly M., Koyama Y., Onoe H., Watanabe Y. Mapping of prostaglandin E2 binding sites in rat brain using quantitative autoradiography. Brain Res. 1992 May 29;581(2):292–298. doi: 10.1016/0006-8993(92)90720-t. [DOI] [PubMed] [Google Scholar]
  40. McCoshen J. A., Hoffman D. R., Kredentser J. V., Araneda C., Johnston J. M. The role of fetal membranes in regulating production, transport, and metabolism of prostaglandin E2 during labor. Am J Obstet Gynecol. 1990 Nov;163(5 Pt 1):1632–1640. doi: 10.1016/0002-9378(90)90642-k. [DOI] [PubMed] [Google Scholar]
  41. McGiff J. C., Terragno N. A., Strand J. C., Lee J. B., Lonigro A. J., Ng K. K. Selective passage of prostaglandins across the lung. Nature. 1969 Aug 16;223(5207):742–745. doi: 10.1038/223742b0. [DOI] [PubMed] [Google Scholar]
  42. Moncada S., Korbut R., Bunting S., Vane J. R. Prostacyclin is a circulating hormone. Nature. 1978 Jun 29;273(5665):767–768. doi: 10.1038/273767a0. [DOI] [PubMed] [Google Scholar]
  43. Morita I., Smith W. L., DeWitt D. L., Schindler M. Expression-activity profiles of cells transfected with prostaglandin endoperoxide H synthase measured by quantitative fluorescence microscopy. Biochemistry. 1995 May 30;34(21):7194–7199. doi: 10.1021/bi00021a034. [DOI] [PubMed] [Google Scholar]
  44. Neri Serneri G. G., Gensini G. F., Abbate R., Prisco D., Rogasi P. G., Castellani S., Casolo G. C., Fazi A., Fantini F., Di Donato M. Impaired cardiac PGI2 and PGE2 biosynthesis in patients with angina pectoris. Am Heart J. 1986 Sep;112(3):472–478. doi: 10.1016/0002-8703(86)90509-0. [DOI] [PubMed] [Google Scholar]
  45. Neri Serneri G. G., Gensini G. F., Abbate R., Prisco D., Rogasi P. G., Castellani S., Casolo G. C., Matucci M., Fantini F., Di Donato M. Spontaneous and cold pressor test-induced prostaglandin biosynthesis by human heart. Am Heart J. 1985 Jul;110(1 Pt 1):50–55. doi: 10.1016/0002-8703(85)90513-7. [DOI] [PubMed] [Google Scholar]
  46. Nowak J., Kaijser L., Wennmalm A. Cardiac prostaglandin formation in man. Adv Myocardiol. 1980;1:323–328. [PubMed] [Google Scholar]
  47. Piper P. J., Vane J. R., Wyllie J. H. Inactivation of prostaglandins by the lungs. Nature. 1970 Feb 14;225(5233):600–604. doi: 10.1038/225600a0. [DOI] [PubMed] [Google Scholar]
  48. Quiroga J., Prieto J. Liver cytoprotection by prostaglandins. Pharmacol Ther. 1993;58(1):67–91. doi: 10.1016/0163-7258(93)90067-N. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Roseman T. J., Yalkowsky S. H. Physicochemical properties of prostaglandin F2 alpha (tromethamine salt): solubility behavior, surface properties, and ionization constants. J Pharm Sci. 1973 Oct;62(10):1680–1685. doi: 10.1002/jps.2600621021. [DOI] [PubMed] [Google Scholar]
  50. Seyberth H. W., Königer S. J., Rascher W., Kühl P. G., Schweer H. Role of prostaglandins in hyperprostaglandin E syndrome and in selected renal tubular disorders. Pediatr Nephrol. 1987 Jul;1(3):491–497. doi: 10.1007/BF00849259. [DOI] [PubMed] [Google Scholar]
  51. Seyberth H. W., Rascher W., Schweer H., Kühl P. G., Mehls O., Schärer K. Congenital hypokalemia with hypercalciuria in preterm infants: a hyperprostaglandinuric tubular syndrome different from Bartter syndrome. J Pediatr. 1985 Nov;107(5):694–701. doi: 10.1016/s0022-3476(85)80395-4. [DOI] [PubMed] [Google Scholar]
  52. Sri Kantha S., Matsumura H., Kubo E., Kawase K., Takahata R., Serhan C. N., Hayaishi O. Effects of prostaglandin D2, lipoxins and leukotrienes on sleep and brain temperature of rats. Prostaglandins Leukot Essent Fatty Acids. 1994 Aug;51(2):87–93. doi: 10.1016/0952-3278(94)90083-3. [DOI] [PubMed] [Google Scholar]
  53. Stjernschantz J., Bito L. Z. The ocular effects of eicosanoids and other autacoids: historic background and the need for a broader perspective. Prog Clin Biol Res. 1989;312:1–13. [PubMed] [Google Scholar]
  54. Suzuki F., Hayashi H., Hayaishi O. Transport of prostaglandin D2 into brain. Brain Res. 1986 Oct 22;385(2):321–328. doi: 10.1016/0006-8993(86)91079-6. [DOI] [PubMed] [Google Scholar]
  55. Ulmann A., Silvestre L., Chemama L., Rezvani Y., Renault M., Aguillaume C. J., Baulieu E. E. Medical termination of early pregnancy with mifepristone (RU 486) followed by a prostaglandin analogue. Study in 16,369 women. Acta Obstet Gynecol Scand. 1992 May;71(4):278–283. doi: 10.3109/00016349209021052. [DOI] [PubMed] [Google Scholar]
  56. Walenga R. W., Kuhn D. C., Stuart M. J. Trans-placental transport and metabolism of carbacyclin by perfused human placental in vitro. Prostaglandins. 1989 Jan;37(1):121–134. doi: 10.1016/0090-6980(89)90036-1. [DOI] [PubMed] [Google Scholar]
  57. Wolfson B., Pickett S., Scott N. E., DeKernion J. B., Rajfer J. Intraurethral prostaglandin E-2 cream: a possible alternative treatment for erectile dysfunction. Urology. 1993 Jul;42(1):73–75. doi: 10.1016/0090-4295(93)90345-b. [DOI] [PubMed] [Google Scholar]
  58. Ziai N., Dolan J. W., Kacere R. D., Brubaker R. F. The effects on aqueous dynamics of PhXA41, a new prostaglandin F2 alpha analogue, after topical application in normal and ocular hypertensive human eyes. Arch Ophthalmol. 1993 Oct;111(10):1351–1358. doi: 10.1001/archopht.1993.01090100059027. [DOI] [PubMed] [Google Scholar]
  59. Zusman R. M., Spector D., Caldwell B. V., Speroff L., Schneider G., Mulbow P. J. The effect of chronic sodium loading and sodium restriction on plasma prostaglandin A, E, and F concentrations in normal humans. J Clin Invest. 1973 May;52(5):1093–1098. doi: 10.1172/JCI107274. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES