Naslov
The effects of prolonged alcohol and gabapentin treatment on HEK 293 cells, non-transfected or stably transfected with recombinant GABA-A receptors

Autori
Moric, Marina ; Kuzman, Boris ; Malesevic, Marina ; Svob Strac, Dubravka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Periodicum Biologorum, Vol. 115, Suppl 3 / Vitale, Branko - Zagreb : Hrvatsko prirodoslovno društvo ; Institut Ruđer Bošković ; Laser Plus, 2013, 83-83

Skup
7th Croatian Congress of Pharmacology with International Participation

Mjesto i datum
Zagreb, Hrvatska, 18.09.2013. - 21.09.2013

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
alcohol; gapabentin; prolonged treatment; HEK 293 cells; recombinant GABA-A receptors

Sažetak
Introduction: Gabapentin, structural analogue of GABA with anticonvulsant properties, showed some positive effects in alcoholism treatment. The precise mechanisms of action of both gabapentin and alcohol are still not clear, although various data indicate that GABA-A receptors mediate acute and chronic effects of alcohol. As neurotoxic consequences of alcohol consumption are common and several reports suggest potential neuroprotective action of gabapentin, the aim of our study was to investigate possible protective ability of gabapentin in alcohol-induced neurotoxicity. Materials and methods: Human embryonic kidney (HEK) 293 cells, non-transfected and stably transfected with alpha1beta2gamma2s GABA-A receptors, were exposed for 96 h to 100 microM alcohol, alone or in combination with 1 microM gabapentin. A trypan blue exclusion assay was performed to assess cell viability. Cell membrane preparations 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. Results: Observed cytotoxic effects of alcohol were reduced by simultaneous gabapentin treatment. Alcohol enhanced the number of benzodiazepine binding sites on recombinant GABA-A receptors without affecting their affinity and reduced GABA- induced potentiation of benzodiazepine binding, suggesting allosteric uncoupling of receptor binding sites. Gabapentin did not affect the number of benzodiazepine binding sites, but restored normal functional interactions of GABA-A receptor binding sites. Conclusions: Although our findings support the hypothesis of GABA-A receptor involvement in the actions of gabapentin, further studies should investigate whether functional recovery of GABA-A receptor binding sites is related to the observed gabapentin protection against the alcohol-induced cytotoxicity.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA