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Regulatory volume decrease after swelling induced by urea in fibroblasts: prominent role of organic osmolytes

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Abstract

Cell swelling, regulatory volume decrease (RVD), volume-sensitive Cl− (Cl− swell) current and taurine efflux after exposure to high concentrations of urea were characterized in fibroblasts Swiss 3T3, and results compared to those elicited by hyposmotic (30%) swelling. Urea 70, 100, and 150 mM linearly increased cell volume (8.25%, 10.6%, and 15.7%), by a phloretin-inhibitable process. This was followed by RVD by which cells exposed to 70, 100, or 150 mM urea recovered 27.6%, 38.95, and 74.1% of their original volume, respectively. Hyposmolarity (30%) led to a volume increase of 25.9% and recovered volume in 32.5%. 3H-taurine efflux was increased by urea with a sigmoid pattern, as 9.5%, 18.9%, 71.5%, and 89% of the labeled taurine pool was released by 70, 100, 150, or 200 mM urea, respectively. Only about 11% of taurine was released by 30% hyposmolarity reduction in spite of the high increase in cell volume. Urea-induced taurine efflux was suppressed by NPPB (100 μM) and markedly reduced by the tyrosine kinase-general blocker AG18. The Cl− swell current was more rapidly activated and higher in amplitude in the hyposmotic than in the isosmotic/urea condition (urea 150 mM), but this was not sufficient to accomplish an efficient RVD. These results showed that at similar volume increase, cells swollen by urea showed higher taurine efflux, lower Cl− swell current and more efficient RVD, than in those swollen by hyposmolarity. The correlation found between RVD efficiency and taurine efflux suggest a prominent role for organic over ionic osmolytes for RVD evoked by urea in isosmotic conditions.

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Acknowledgments

We deeply acknowledge the valuable technical assistance of Ms. Claudia Peña-Segura. This work was supported in part by grants No. 209507 from DGAPA, UNAM, and 46465 from CONACYT, México.

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Authors and Affiliations

  1. Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, Circuito Exterior, Mexico, DF, 04510, Mexico

    Alejandra López-Domínguez, Gerardo Ramos-Mandujano, Erika Vázquez-Juárez & Herminia Pasantes-Morales

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  1. Alejandra López-Domínguez
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  2. Gerardo Ramos-Mandujano
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  3. Erika Vázquez-Juárez
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  4. Herminia Pasantes-Morales
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Correspondence to Herminia Pasantes-Morales.

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López-Domínguez, A., Ramos-Mandujano, G., Vázquez-Juárez, E. et al. Regulatory volume decrease after swelling induced by urea in fibroblasts: prominent role of organic osmolytes. Mol Cell Biochem 306, 95–104 (2007). https://doi.org/10.1007/s11010-007-9558-7

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  • DOI: https://doi.org/10.1007/s11010-007-9558-7

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