Abstract
Early sea urchin embryos are sensitive to agonists and antagonists of transmitter receptors, both metabotropic and channel ones. In this work, we studied mechanisms of the cytostatic action of cyproheptadine and haloperidol–antagonists of serotonin 5HT2 receptors and dopamine D2 receptors, respectively. For this purpose, we employed the model of the blockade of the first cleavage division in sea urchin, which allows quantifying the effects of embryotoxic substances. The action of haloperidol and cyproheptadine is mediated by the effects on cytoskeleton elements. Both antagonists caused an increase in the degree of polymerization of the actin cytoskeleton, both in the cortical layer and in the cytoplasm. In addition, both antagonists affected the tubulin cytoskeleton: haloperidol predominantly disturbed spatial organization of the mitotic spindle, while cyproheptadine caused a complete depolymerization of tubulin and arrest of mitotic processes. The results indicate that cytostatic effects of dopamine and serotonin antagonists on cleavage divisions of sea urchin embryos are mediated by similar and/or crosstalk molecular mechanisms but also have significant differences that require further research.
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ACKNOWLEDGMENTS
The work was supported by the Russian Academy of Sciences and Serbian Academy of Art and Science (joint program Neurotransmitters – Ontogenetic and Neurobiological Aspects). The work was conducted in the frames of the Government basic research program no. 0108-2019-0003 (Institute of Developmental Biology, RAS). N.D.A., M.L.A., and S.Y.B. carried out the work using the equipment of the Core Center of the Institute of Developmental Biology RAS.
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All procedures were performed in accordance with the European Communities Council Directive (November 24, 1986; 86/609/EEC) and the Declaration on humane treatment of animals. The Protocol of experiments was approved by the Commission on Bioethics of the Koltzov Institute of Developmental Biology RAS, Moscow, Russia.
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Nikishin, D.A., Malchenko, L.A., Milošević, I. et al. Effects of Haloperidol and Cyproheptadine on the Cytoskeleton of the Sea Urchin Embryos. Biochem. Moscow Suppl. Ser. A 14, 249–254 (2020). https://doi.org/10.1134/S1990747820020087
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DOI: https://doi.org/10.1134/S1990747820020087