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

作者：Run Lu, Norifumi Kanai, Yi Bao, V. L. Schuster · 发表于：Journal of Clinical Investigation · 年份：1996 · DOI：10.1172/jci118897 · 被引用次数：242 · 研究领域：Inflammatory mediators and NSAID effects、Drug Transport and Resistance Mechanisms、Peroxisome Proliferator-Activated Receptors

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 Ј 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 PGE 1 , PGE 2 , PGD 2 , PGF 2 ␣ and, to a lesser degree TXB 2 .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.( J. Clin.Invest.1996.98:1142-1149.)Key words: prostaglandins • carrier proteins • biological transport • molecular cloningWe have postulated three possible roles for PGT (36).First, PGT might mediate the efflux of newly-synthesized PGs from cells.Although PGs apparently do gain access to the cytoplasmic compartment (37), it is unclear whether a carrier is necessary for their subsequent efflux into the extracytoplasmic space.Second, PGT might mediate epithelial PG transpo...