Liposome-entrapped GABA modulates the expression of nNOS in NG108-15 cells

- GABA (γ-aminobutyric acid) - containing liposomes (GL) show the slow release of GABA.
- Cells treated with GL showed an increase in neuronal nitric oxide synthase expression and intracellular nitric oxide.
- The increase in nNOS expression was accompanied by a decrease in protein inhibitor of nNOS (PIN) expression.
- Released GABA may cause activation in GABAA receptors.
- Alterations in PIN expression may be a consequence of GABAA receptor activation.

BackgroundLiposomes are concentric lipid vesicles that allow a sustained release of entrapped substances. GABA (γ-aminobutyric acid) is the most prevalent inhibitory neurotransmitter in the central nervous system.New methodUsing GABA-containing liposomes (GL) prepared by the freeze-thawing method, we determined the effect of sustained release of GABA on expression of neuronal nitric oxide synthase (nNOS) and GABAA receptor (GABAAR) in an in vitro neuronal model.ResultsNeuronal cell line NG108-15 treated with different doses of GL during 24 h showed an increase in expression of GABAAR (54 and 50% with 10 and 20 ng doses, respectively) and nNOS (138, 157 and 165% with 20, 50 and 100 ng doses, respectively) compared with cells treated with empty liposomes (EL). Additionally, cells treated with 50 ng of GL showed an increase in GABAAR (23%) after 1 h followed by an increase in nNOS (55, 46 and 55%) at 8, 12 and 24 h time points, respectively. Immunofluorescence experiments confirmed an increase in nNOS (134%) and basal intracellular levels of nitric oxide (84%) after GL treatment. Further, treatment of cells with GL showed a decrease in expression of a protein inhibitor of nNOS (PIN) (26, 66 and 57% with 20, 50 and 100 ng doses respectively) compared with control.Comparison with existing methodsThis is first demonstration for the development of GL that allows sustained slow release of this neurotransmitter.ConclusionThese results suggest that a slow release of GABA can change the expression of nNOS possibly via alteration in PIN levels in neuronal cells.