Organic anion transporting polypeptides expressed in liver and brain mediate uptake of microcystin

Microcystins are toxins produced by freshwater cyanobacteria. They are cyclic heptapeptides that exhibit hepato- and neurotoxicity. However, the transport systems that mediate uptake of microcystins into hepatocytes and across the blood-brain barrier have not yet been identified. Using the Xenopus laevis oocyte expression system we tested whether members of the organic anion transporting polypeptide superfamily (rodent: Oatps; human: OATPs) are involved in transport of the most common microcystin variant microcystin-LR by measuring uptake of a radiolabeled derivative dihydromicrocystin-LR. Among the tested Oatps/OATPs, rat Oatp1b2, human OATP1B1, human OATP1B3, and human OATP1A2 transported microcystin-LR 2- to 5-fold above water-injected control oocytes. This microcystin-LR transport was inhibited by co-incubation with the known Oatp/OATP substrates taurocholate (TC) and bromosulfophthalein (BSP). Microcystin-LR transport mediated by the human OATPs was further characterized and showed saturability with increasing microcystin-LR concentrations. The apparent K(m) values amounted to 7 +/- 3 microM for OATP1B1, 9 +/- 3 microM for OATP1B3, and 20 +/- 8 microM for OATP1A2. No microcystin-LR transport was observed in oocytes expressing Oatp1a1, Oatp1a4, and OATP2B1. These results may explain some of the observed organ-specific toxicity of microcystin-LR. Oatp1b2, OATP1B1, and OATP1B3 are responsible for microcystin transport into hepatocytes, whereas OATP1A2 mediates microcystin-LR transport across the blood-brain barrier

A gharial from the Oligocene of Puerto Rico: transoceanic dispersal in the history of a non-marine reptile

The Indian gharial (Gavialis gangeticus) is not found in saltwater, but the geographical distribution of fossil relatives suggests a derivation from ancestors that lived in, or were at least able to withstand, saline conditions. Here, we describe a new Oligocene gharial, Aktiogavialis puertoricensis, from deltaic–coastal deposits of northern Puerto Rico. It is related to a clade of Neogene gharials otherwise restricted to South America. Its geological and geographical settings, along with its phylogenetic relationships, are consistent with two scenarios: (i) that a single trans-Atlantic dispersal event during the Tertiary explains the South American Neogene gharial assemblage and (ii) that stem gharials were coastal animals and their current restriction to freshwater settings is a comparatively recent environmental shift for the group. This discovery highlights the importance of including fossil information in a phylogenetic context when assessing the ecological history of modern organisms