Učinci dugotrajne primjene alkohola i gabapentina na rekombinantne GABAA receptore u kulturi stanica

master's thesis

• Title (english): The effects of long-term alcohol and gabapentin exposure on recombinant GABAA receptors in cell culture
• Author: Marina Malešević
• Mentor: Dubravka Švob Štrac (mentor)
• Mentor: Domagoj Đikić (mentor)
• Committee member: Domagoj Đikić (predsjednik povjerenstva)
• Committee member: Dubravka Švob Štrac (član povjerenstva)
• Committee member: Ivana Ivančić Baće (član povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2012-09-26, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Dugotrajna primjena alkohola izaziva promjene GABAA receptora koje se povezuju sa razvojem alkoholizma. Gabapentin pokazuje pozitivne učinke u liječenju alkoholizma. Mehanizmi djelovanja gabapentina, kao i alkohola nisu jasni. Citotoksični učinak dugotrajnog izlaganja stanica HEK 293, transficiranih receptorima α1β2γ2s GABAA tipa, 100 mM alkoholu smanjen je ustezanjem alkohola, kao i dugotrajnom primjenom 1 μM gabapentina. Produljeni tretman alkoholom povećao je broj benzodiazepinskih veznih mjesta i smanjio alosteričku povezanost receptorskih veznih mjesta, koji se ustezanjem alkohola vraćaju na kontrolne razine. Gabapentin nije utjecao na broj benzodiazepinskih veznih mjesta, ali je poništio slabljenje funkcionalnih interakcija receptorskih veznih mjesta izazvano alkoholom. Rezultati upućuju da dugotrajna primjena alkohola izaziva slične promjene receptora GABAA tipa kao i produljeno izlaganje benzodiazepinima, koji također izazivaju ovisnost. Rezultati podržavaju pretpostavku o uključenosti receptora GABAA tipa u djelovanje gabapentina. Daljnja istraživanja trebala bi utvrditi da li se protektivno djelovanje gabapentina protiv citotoksičnog učinka alkohola ostvaruje putem jačanja funkcionalne alosteričke povezanosti receptorskih veznih mjesta.

Abstract (english)

Prolonged exposure of GABAA receptors to alcohol triggers changes associated with the development of alcoholism. Gabapentin shows positive effects in alcoholism treatment. The mechanisms of action of both, gabapentin and alcohol, are not clear. Cytotoxic effect of prolonged exposure of HEK 293 cells, expressing α1β2γ2s GABAA receptors, to 100 mM alcohol was reduced by alcohol withdrawal and 1 μM gabapentin treatment. Chronic alcohol treatment induced an increase in the number of benzodiazepine binding sites and allosteric uncoupling, which were counteracted by alcohol withdrawal. Gabapentin did not affect the number of benzodiazepine binding sites, but restored their normal functional interactions. The results suggest that prolonged alcohol treatment induces similar changes of GABAA receptors as prolonged exposure to benzodiazepines, which also produce dependence. Results support the hypothesis of involvement of GABAA receptors in the actions of gabapentin. Further studies should investigate whether receptor functional coupling underlies the protective effect of gabapentin against the alcohol cytotoxic effects.

• Keywords: alkohol; dugotrajna primjena; gabapentin; kultura stanica HEK 293; rekombinantni receptori GABAA
• Keywords (english): alcohol; long-term treatment; recombinant GABAA receptors; HEK 293 cell culture; gabapentin
• Language: croatian
• URN:NBN: urn:nbn:hr:217:220330
• Study programme: Title: Experimental Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra eksperimentalne biologije (magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2017-05-02 09:33:56