Effect of Dibutyryl Cyclic AMP on the Kinetics of myo‐Inositol Transport in Cultured Astrocytes

Abstract

Dibutyryl cyclic AMP (dBcAMP) is known to induce maturation and differentiation in astrocytes. As myo-inositol is an important osmoregulator in astrocytes, we examined the effects of maturation and biochemical differentiation on the kinetic properties of myo-inositol transport. Treatment of astrocytes with dBcAMP significantly decreased the V max of myo-inositol uptake, but the effect on K m was not significant. The myo-inositol content of astrocytes was significantly decreased in cells treated for 5 days with dBcAMP as compared with untreated controls. Maximum suppression of myo-inositol uptake occurred 7 days after exposure of astrocytes to dBcAMP; this was gradually reversible when dBcAMP was removed from the medium. After exposure to hypertonic medium for 6 h, mRNA expression of the myo-inositol co-transporter was diminished by ϳ36% in astrocytes treated with dBcAMP as compared with untreated cells. It appears that myo-inositol transporters in astrocytes treated with dBcAMP are either decreased in number or inactivated during maturation and differentiation, suggesting that the stage of differentiation and biochemical maturation of astrocytes is an important factor in osmoregulation.

Molecular aspects of medicine: from experimental to clinical hepatology

“…There is a good correlation between the extent of these 1 H-MRS-changes and the clinical severity of HE (Ross et al, 1996;Laubenberger et al, 1997). In line with this, cultured astrocytes swell under the influence of ammonia (Norenberg et al, 1991) in a methionine sulfoximine-sensitive way (Isaaks et al, 1999). However, ammonia may not be the only mechanism by which astrocyte swelling is triggered in HE, because astrocyte swelling also occurs in vitro under the influence of hyponatremia, some neurotransmitters, TNFa, and benzodiazepines (for review see H€ aussinger et al, 2000a).…”

Characterization of the Expression and Regulation of Genes Necessary for myo-Inositol Biosynthesis and Transport in the Seminiferous Epithelium1

“…In cultured astrocytes treated with dbcAMP, there is a downregulation of Slc5a3 expression [32], and it was suggested by the authors that dbcAMP is important for maturation of astrocytes and that the biochemical stage is important for osmoregulation in astrocytes [32]. Primary mouse Sertoli cells were treated with either FSH or dbcAMP, and a significant increase in transcription of the Slc5a3 gene was observed at all time points.…”

Hypoosmotic swelling and ammonia increase oxidative stress by NADPH oxidase in cultured astrocytes and vital brain slices

“…4B). Whereas at a long-term time scale glutamine accumulation may sustain astrocyte swelling because of osmotic forces and induction of the mitochondrial permeability transition (Isaacks et al, 1999;Jayakumar et al, 2006;Norenberg et al, 1991), NH 4 1 influx via K 1 transport pathways may account for the astrocyte swelling starting instantaneously after exposure to ammonia (Nagaraja and Brookes, 1998). It is well conceivable that astrocyte swelling contributes to the NADPH oxidasedependent ROS production by ammonia.…”