engleski

The effects of combined gabapentin and alcohol treatment on HEK 2932 cell culture

Gabapentin, an analogue of GABA, was originally developed to treat epilepsy. However, this anticonvulsive drug demonstrated some positive effects in the treatment of alcohol addiction and withdrawal. Recent reports also indicated potential neuroprotective and antioxidant effects of gabapentin. Although different receptors are suggested to be implicated in its action, the precise mechanisms are still not known. As neurotoxic consequences of high alcohol consumption are common, the aim of our study was to investigate possible protective ability of gabapentin in alcohol-induced citotoxicity. Human embryonic kidney (HEK) 293 cells, non- transfected and stably transfected with alpha1beta2gamma2S GABA-A receptors, were exposed to various concentrations of alcohol and gabapentin for different periods of time. A trypan blue exclusion assay was performed to assess cell viability. Membrane preparations of stably transfected HEK 293 cells treated with 100 mM alcohol in combination with 1 microM gabapentin for 96h were used in [3H]flunitrazepam binding studies to determine the number and affinity of benzodiazepine binding sites, and their allosteric interactions with GABA binding sites. Observed cytotoxic effects of 100 mM alcohol were reduced by simultaneous 1microM gabapentin treatment only in HEK 293 stably transfected with alpha1beta2gamma2S GABA-A receptors. On recombinant GABA-A receptors alcohol induced up- regulation of benzodiazepine binding sites without affecting their affinity. In the same time, alcohol decreased GABA-induced potentiation of benzodiazepine binding, suggesting allosteric uncoupling of receptor binding sites. Simultaneous gabapentin treatment did not change the number of benzodiazepine binding sites, but restored normal functional interactions of GABA-A receptor binding sites. Our findings support the hypothesis that gabapentin exert at least some of its actions via GABA-A receptors. However, further studies are necessary to elucidate whether functional recovery of GABA-A receptor binding sites following gabapentin treatment is related to its protective effects against the alcohol-induced cytotoxicity in HEK 293 cells.

alcohol; gabapentin; HEK 293 culture

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