The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Mechanism of prostaglandin E2 transport across the plasma membrane of HeLa cells and Xenopus oocytes expressing the prostaglandin transporter " PGT".

We recently identified a novel prostaglandin transporter called PGT (Kanai, N., Lu, R., Satriano, J. A., Bao, Y., Wolkoff, A. W., and Schuster, V. L. (1995) Science 268, 866-869). Based on initial functional studies, we have hypothesized that PGT might mediate the release of newly synthesized prostaglandins (PG), epithelial transport of PGs, or metabolic clearance of PGs. Here we examined the mechanism of PGT transport as expressed in HeLa cells and Xenopus oocytes, using isotopic PG influx and efflux studies. In both native HeLa cells and oocytes, cell membranes were poorly permeable to PGs. In contrast, in oocytes injected with PGT mRNA, the PG influx permeability coefficient was 90-157 times that of oocytes injected with water. The rank order substrate profile was PGF2alpha approximately PGE2 > TXB2 >> 6 keto-PGF1alpha. PG influx displayed an overshoot with rapid accumulation of tracer PGE2, followed by a gradual return to baseline. Based on estimated oocyte volumes, the PGT-mediated accumulation of PGE2 reached steady state at intra-oocyte concentrations 25-fold higher than the external media. The accumulation of PG was not due to intracellular binding or metabolism. PGT-mediated uptake was ATP- and temperature-dependent, but not sodium-dependent, and was inhibited by disulfonic stilbenes, niflumic acid, and the thiol reactive anion MTSES (Na(2-sulfonatoethyl)methanethiosulfonate). [3H]PGE2 efflux from PGT-transfected HeLa cells was stimulated by external (trans) PGE2 in a dose-dependent fashion and was inhibited by bromcresol green and 4,4'-diisothiocyanatostilbene-2,2'-disulfonate. Membrane depolarization inhibited uptake of [3H]PGE2, consistent with a model of net outward movement of negative charge during the translocation event. These findings suggest that PGT mediates [3H]PGE2 accumulation via obligatory, electrogenic anion exchange.[1]

References

 
WikiGenes - Universities