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The increasing presence of ZnO nanoparticles (NPs) in consumer products may be having a dramatic impact in aquatic environments. The evaluation of ZnO NP toxicity represents a great challenge. This study aimed at evaluating the cytotoxic effect of micro- and nanosized ZnO in a fish and a mammalian hepatoma cell line. A detailed characterisation of the particles in exposure media showed that ZnO NPs formed large aggregates. ZnO cytotoxicity was evaluated with a battery of in vitro assays including LUCS, a new approach based on DNA alteration measurements. In fish cells, ZnO NP aggregates contributed substantially to the cytotoxic effects whereas toxicity in the human cells appeared to be mainly produced by the dissolved fraction. ROS production did not contribute to the observed cytotoxicity. This work also showed that measuring concentrations of NPs is essential to understand the mechanisms underlying their toxicity. [ABSTRACT FROM AUTHOR]

[³H]SSR-1494 15 is the first tritiated nonpeptide vasopressin V1b receptor (V1bR) antagonist Iigand. It was used for studying rodent (mouse, rat, hamster) and human V1bR from native or recombinant origin. Moreover, a close comparison between the human and the mouse V1bR was performed using SSR-149415/[³H]SSR-149415 in binding and functional studies in vitro. [³H]SSR-149415 binding was time-dependent, reversible, and saturable. Scatchard plot analysis gave a single class of high-affinity binding sites with apparent equilibrium dissociation constant (Kd) ~1 nM and maximum binding density (Bmax) values from 7,000 to 300,000 sites/cell according to the cell line. In competition experiments, [³H]SSR-149415 binding was stereospecific and dose-dependently displaced by reference peptide and nonpeptide arginine vasopressin (AVP)/OT ligands following a V1b rank order of affinity: SSR-149415 = AVP > dCha > dPen > dPal > dDavp > SSR-126768A > SR-49059 > SSR-149424 > OT > SR-121463B. Species differences between human, rat, mouse, and hamster V1bR were observed. Autoradiography studies with [³H]SSR-149415 on rat and human pituitary showed intense specific labeling confined to corticotroph cells and absence of labeling in the other tissues examined. SSR-149415 potently and stereospecifically antagonized the AVP-induced inositol phosphate production and intracellular Ca2+ increase (EC50 from 1.83 to 3.05 nM) in recombinant cell lines expressing either the mouse or the human V1bR. AVP (10-7 M) exposure of AtT20 cells expressing mouse or human EGFP-tagged V1bR induced their rapid internalization. Preincubation with 10-6 M SSR-149415 counteracted the internalization process. Moreover, recycling of internalized receptors was observed upon 10-6 M SSR-149415 treatment. Thus SSR-149415/[³H]SSR-149415 are unique tools for studying animal and human V1bR. [ABSTRACT FROM AUTHOR]

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