“…In contrast, the apical surfaces of the epithelial cells lining the external body tissues, including the skin, fin, gill, and upper regions of the gastrointestinal tract are faced with much greater osmotic challenges as the external osmolality of <5 mosmol/kg H 2 O found in FW is increased to over 1,000 mosmol/kg H 2 O when fish move to SW. As might be expected, epithelial cells in these tissues must accumulate even higher concentrations of organic osmolytes, including inositol, to maintain their cell volume and, consequently, the integrity of the epithelium. Cellular accumulation of inositol can either be the result of secondary active transport across the plasma membrane by the actions of carriers, such as the sodium myo-inositol transporter (SMIT) and/or the proton myo-inositol transporter (HMIT), as has been reported for various mammalian tissues, including the kidney and brain (6, 12, 28, 41), or can be the result of de novo synthesis from glucose 6-phosphate (36, 43). In the mammalian studies so far reported, neuronal tissues appear to accumulate relatively high concentrations of free inositol (20, 46, 47); however, the brain generally expresses relatively low levels of MIPS mRNA (19), suggesting accumulation via SMIT/HMIT may be more physiologically important than de novo synthesis.…”