Effects of ammonia exposition on glioma cells: Changes in cell volume and organic osmolytes studied by diffusion-weighted and high-resolution NMR spectroscopy

NH4Cl (10 mM) caused a sustained increase in the cell volume in immobilized , perfused F98 glioma cells to approx. 125% of control after 3 h, as measur ed by diffusion-weighted H-1 NMR spectroscopy. Concomitantly, the glutamine (Gln) concentration increased by 130%, accompanied by a marked decrease in cytosolic osmolytes, i.e. myo-inositol and taurine, determined from H-1 NM R spectra of PCA extracts. Inhibition of Gin synthetase partially prevented the increase in water content. While losses of organic osmolytes are also observed under hypotonic conditions, the rapid cell swelling is followed by the regulatory cell volume decrease (RVD), and is accompanied by decreased cytosolic Gin. We suggest that the rise in intracellular osmolarity, which is attributed to NH4Cl metabolism to Gin, but also to alanine (Ala), is no t compensated by the release of other osmolytes, and causes cell swelling w ithout RVD. Copyright (C) 2000 S. Karger AG, Basel.