Volume-activated trimethylamine oxide efflux in red blood cells of spiny dogfish (Squalus acanthias)

The aims of this study were to determine the pathway of swelling-activated trimethylamine oxide (TMAO) efflux and its regulation in spiny dogfish (Squ alus acanthias) red blood cells and compare the characteristics of this eff lux pathway with the volume-activated osmolyte (taurine) channel present in erythrocytes of fishes. The characteristics of the TMAO efflux pathway wer e similar to those of the taurine efflux pathway. The swelling-activated ef fluxes of both TMAO and taurine were significantly inhibited by known anion transport inhibitors (DIDS and niflumic acid) and by the general channel i nhibitor quinine. Volume expansion by hypotonicity, ethylene glycol, and di ethyl urea activated both TMAO and taurine effluxes similarly. Volume expan sion by hypotonicity, ethylene glycol, and diethyl urea also stimulated the activity of tyrosine kinases p72syk and p56lyn, although the stimulations by the latter two treatments were less than by hypotonicity. The volume act ivations of both TMAO and taurine effluxes were inhibited by tyrosine kinas e inhibitors, suggesting that activation of tyrosine kinases may play a rol e in activating the osmolyte effluxes. These results indicate that the volu me-activated TMAO efflux occurs via the organic osmolyte (taurine) channel and may be regulated by the volume activation of tyrosine kinases.