Molecular characterization of human and rat organic anion transporter OATP-D

Am J Physiol Renal Physiol. 2003 Dec;285(6):F1188-97. doi: 10.1152/ajprenal.00402.2002.

Abstract

We have isolated and characterized a novel human and rat organic anion transporter subtype, OATP-D. The isolated cDNA from human brain encodes a polypeptide of 710 amino acids (Mr 76,534) with 12 predicted transmembrane domains. The rat clone encodes 710 amino acids (Mr 76,821) with 97.6% amino acid sequence homology with human OATP-D. Human and rat OATP-D have moderate amino acid sequence homology with LST-l/rlst-1, the rat oatp family, the prostaglandin transporter, and moatl/MOAT1/KIAA0880/OATP-B. Phylogenetic tree analysis revealed that OATP-D is branched in a different position from all known organic anion transporters. OATP-D transports prostaglandin E1 (Km 48.5 nM), prostaglandin E2 (Km 55.5 nM), and prostaglandin F2,, suggesting that, functionally, OATP-D encodes a protein that has similar characteristics to those of the prostaglandin transporter. Rat OATP-D also transports prostaglandins. The expression pattern of OATP-D mRNA was abundant mainly in the heart, testis, brain, and some cancer cells. Immunohistochemical analysis further revealed that rat OATP-D is widely expressed in the vascular, renal, and reproductive system at the protein level. These results suggest that OATP-D plays an important role in translocating prostaglandins in specialized tissues and cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alprostadil / metabolism*
  • Amino Acid Sequence
  • Animals
  • Anions / metabolism
  • Blotting, Northern
  • Brain Chemistry / physiology
  • Burkitt Lymphoma
  • DNA, Complementary
  • Dinoprostone / metabolism*
  • HL-60 Cells
  • HeLa Cells
  • Humans
  • K562 Cells
  • Leukemia, Lymphoid
  • Lung Neoplasms
  • Melanoma
  • Molecular Sequence Data
  • Oocytes
  • Organic Anion Transporters / genetics*
  • Organic Anion Transporters / metabolism*
  • RNA, Messenger / analysis
  • Rats
  • Xenopus laevis

Substances

  • Anions
  • DNA, Complementary
  • Organic Anion Transporters
  • RNA, Messenger
  • SLCO3A1 protein, human
  • Slco3a1 protein, rat
  • Alprostadil
  • Dinoprostone