ABSTRACT
Organic anion transporting polypeptides (rodent Oatp; human OATP) mediate cellular uptake of numerous organic compounds including xenobiotic toxins into mammalian hepatocytes. In the little skate Leucoraja erinacea a liver-specific Oatp (Oatp1d1, also called sOatp) has been identified and suggested to represent an evolutionarily ancient precursor of the mammalian liver OATP1B1 (human), Oatp1b2 (rat), and OATP1B3 (human). The present study tested whether Oatp1d1 shares functional transport activity of the xenobiotic oligopeptide toxins phalloidin and microcystin with the mammalian liver Oatps/OATPs. The phalloidin analogue [(3)H]-demethylphalloin was taken up into skate hepatocytes with high affinity (Km approximately 0.4 microM), and uptake could be inhibited by phalloidin and a variety of typical Oatp/OATP substrates such as bromosulfophthalein, bile salts, estrone-3-sulfate, cyclosporine A and high concentrations of microcystin-LR (Ki approximately 150 microM). When expressed in Xenopus laevis oocytes Oatp1d1 increased uptake of demethylphalloin (Km approximately 2.2 microM) and microcystin-LR (Km approximately 27 microM) 2- to 3-fold over water-injected oocytes, whereas the alternative skate liver organic anion transporter, the dimeric Ostalpha/beta, exhibited no phalloidin and only minor microcystin-LR transport. Also, the closest mammalian Oatp1d1 orthologue, the human brain and testis OATP1C1, did not show any phalloidin transport activity. These results demonstrate that the evolutionarily ancient Oatp1d1 is able to mediate uptake of cyclic oligopeptide toxins into skate liver. The findings support the notion that Oatp1d1 is a precursor of the liver-specific mammalian Oatps/OATPs and that its transport properties are closely associated with certain forms of toxic liver injury such as for example protein phosphatase inhibition by the water-borne toxin microcystin.
Subject(s)
Hepatocytes/metabolism , Liver/metabolism , Microcystins/metabolism , Organic Anion Transporters/metabolism , Phalloidine/metabolism , Skates, Fish , Animals , Biological Transport/drug effects , Cell Separation , Enzyme Inhibitors/pharmacology , Female , Gene Expression/drug effects , Hepatocytes/drug effects , Humans , Liver/drug effects , Male , Marine Toxins , Microcystins/pharmacology , Oligonucleotides, Antisense/pharmacology , Oocytes/drug effects , Oocytes/metabolism , Organic Anion Transporters/genetics , Species Specificity , Substrate Specificity , Xenopus laevisSubject(s)
Health Services Needs and Demand , Health Services Research , Periodontal Diseases/epidemiology , Periodontal Index , Adolescent , Adult , Dental Calculus/epidemiology , Female , France , Gingival Hemorrhage/epidemiology , Humans , Male , Middle Aged , Periodontal Diseases/therapy , Periodontal Pocket/epidemiologyABSTRACT
Although the gingival index and sulcus bleeding index have been widely used as indicators of periodontal status, there is some disagreement among investigators as to their meaning and significance. A clinical study was undertaken to monitor the occurrence of gingival bleeding, oedema, and change in colour in subjects with and without periodontal disease, and it was found that the combinations of these clinical symptoms often did not correspond exactly with an index score. It is therefore suggested that any study of periodontal disease should be based on fundamental criteria, such as bleeding or oedema, rather than on composite indices.
