Regulatory volume decrease after swelling induced by urea in fibroblasts: prominent role of organic osmolytes |
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Authors: | Alejandra López-Domínguez Gerardo Ramos-Mandujano Erika Vázquez-Juárez Herminia Pasantes-Morales |
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Institution: | (1) Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, Circuito Exterior, Mexico, DF, 04510, Mexico |
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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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Keywords: | Swelling Taurine Volume-sensitive chloride channel |
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