title: Volume-activated trimethylamine oxide efflux in red blood cells of spiny dogfish (Squalus acanthias).
abstract: The aims of this study were to determine the pathway of swelling-activated trimethylamine oxide (TMAO) efflux and its regulation in spiny dogfish (Squalus acanthias) red blood cells and compare the characteristics of this efflux pathway with the volume-activated osmolyte (taurine) channel present in erythrocytes of fishes. The characteristics of the TMAO efflux pathway were similar to those of the taurine efflux pathway. The swelling-activated effluxes of both TMAO and taurine were significantly inhibited by known anion transport inhibitors (DIDS and niflumic acid) and by the general channel inhibitor quinine. Volume expansion by hypotonicity, ethylene glycol, and diethyl urea activated both TMAO and taurine effluxes similarly. Volume expansion 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 activations of both TMAO and taurine effluxes were inhibited by tyrosine kinase inhibitors, suggesting that activation of tyrosine kinases may play a role in activating the osmolyte effluxes. These results indicate that the volume-activated TMAO efflux occurs via the organic osmolyte (taurine) channel and may be regulated by the volume activation of tyrosine kinases.
authors.affiliation: Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Koomoa
authors.forename: M W
authors.initials: MW
authors.lastname: Musch
authors.forename: A V
authors.initials: AV
authors.lastname: MacLean
authors.forename: L
authors.initials: L
authors.lastname: Goldstein
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D004284:Dogfish; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019855:Ethylene Glycol / Q000494:pharmacology; D007038:Hypotonic Solutions / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D017136:Ion Transport / Q000187:drug effects; D008744:Methylamines / Q000378:metabolism*; D009544:Niflumic Acid / Q000494:pharmacology; D009994:Osmolar Concentration; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011803:Quinine / Q000494:pharmacology; D000072377:Syk Kinase; D013654:Taurine / Q000378:metabolism; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D007038:Hypotonic Solutions; D047908:Intracellular Signaling Peptides and Proteins; D008744:Methylamines; D000643:Ammonium Chloride; D013654:Taurine; D009544:Niflumic Acid; C022223:diethylurea; D014508:Urea; D011803:Quinine; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D019855:Ethylene Glycol; C005855:trimethyloxamine; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid