title: Response to hypertonicity in mesothelial cells: role of Na+/myo-inositol co-transporter.
abstract: BACKGROUND
  During peritoneal dialysis, the peritoneal mesothelium is exposed continually to hypertonic dialysates. The purpose of this study is to see if rat mesothelial cells have an osmoregulatory mechanism to adapt to hypertonic environment.
  
  
  METHODS
  The intracellular content of organic osmolytes was measured by HPLC methods. Myo-inositol transport activity was measured by Na+-dependent uptake of [3H]myo-inositol. mRNA abundance for the Na+/myo-inositol co-transporter (SMIT) was examined by Northern and slot-blot analyses.
  
  
  RESULTS
  In isotonic mesothelial cells, only myo-inositol could be detected. After switching to hypertonic medium made by addition of NaCl, myo-inositol content gradually increased and peaked at 48 h after the switch. The myo-inositol content in hypertonic cells increased > 7-fold over the value in isotonic cells. The contents of betaine and glycerophosphorylcholine (GPC) also increased but were less than that of myo-inositol. Sorbitol was not accumulated in this condition. When glucose was used to increase medium osmolality, all of the four osmolytes were increased by hypertonicity (myo-inositol > sorbitol > GPC > betaine). Thus, myo-inositol is the most abundant osmolyte in the mesothelial cells. Na+-dependent myo-inositol uptake in hypertonic cells was approximately 7-fold the uptake in isotonic cells, reaching a maximum 16 h after switching to a hypertonic medium. The uptake rate increased as medium osmolality increased from 300 to 500 mosm/kg. SMIT mRNA rapidly increased after increasing medium osmolality, reaching a maximum 8 h after the switch. The relative increase in the mRNA abundance was approximately 11 times isotonic levels.
  
  
  CONCLUSIONS
  Mesothelial cells respond to extracellular hypertonicity by increasing SMIT mRNA abundance, myo-inositol transport activity and accumulating myo-inositol into the cells.
authors.affiliation: First Department of Medicine, Osaka University School of Medicine, Suita, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuoka
authors.forename: A
authors.initials: A
authors.lastname: Yamauchi
authors.forename: T
authors.initials: T
authors.lastname: Nakanishi
authors.forename: T
authors.initials: T
authors.lastname: Sugiura
authors.forename: H
authors.initials: H
authors.lastname: Kitamura
authors.forename: M
authors.initials: M
authors.lastname: Horio
authors.forename: Y
authors.initials: Y
authors.lastname: Takamitsu
authors.forename: A
authors.initials: A
authors.lastname: Ando
authors.forename: E
authors.initials: E
authors.lastname: Imai
authors.forename: M
authors.initials: M
authors.lastname: Hori
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006982:Hypertonic Solutions; D007294:Inositol / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D008565:Membrane Proteins; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D027981:Symporters; D014882:Water-Electrolyte Balance
chemical_list: D002352:Carrier Proteins; D006360:Heat-Shock Proteins; D006982:Hypertonic Solutions; D008565:Membrane Proteins; D012333:RNA, Messenger; D027981:Symporters; C073884:SLC5A3 protein, human; D007294:Inositol; D012964:Sodium