ISSN:
1471-4159
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Medizin
Notizen:
Abstract : In an earlier study, we demonstrated that chronic ethanol(EtOH) exposure down-regulated the cannabinoid receptors (CB1) in mouse brainsynaptic plasma membrane. In the present study, we investigated the effect ofchronic EtOH on the formation of anandamide (AnNH), an endogenouscannabimimetic compound, and its precursorN-arachidonoylphosphatidylethanolamine (N-ArPE) in SK-N-SH cells thatwere prelabeled with [3H]arachidonic acid. The results indicatethat exposure of SK-N-SH cells to EtOH (100 mM) for 72 hsignificantly increased levels of [3H]AnNH and[3H]N-ArPE (p 〈 0.05) (1.43-fold for[3H]AnNH and 1.65-fold for [3H]N-ArPE). Exposure ofSK-N-SH cells to EtOH (100 mM, 24h) inhibited initially the formationof [3H]AnNH at 24 h, followed by a progressive increase, reaching astatistical significance level at 72 h (p 〈 0.05).[3H]N-ArPE increased gradually to a statistically significant levelafter 48 and 72 h (p 〈 0.05). Incubation with exogenousethanolamine (7 mM) and EtOH (100 mM, 72 h) did not resultin an additive increase in the formation of [3H]AnNH. The formationof [3H]AnNH and [3H]N-ArPE by EtOH was enhanced by theCa2+ ionophore A23187 or by the depolarizing agent veratridine andthe K+ channel blocker 4-aminopyridine. Further, the EtOH-inducedformation of [3H]AnNH and [3H]N-ArPE was inhibited byexogenous AnNH, whereas only [3H]AnNH formation was inhibited bythe CB1 receptor antagonist SR141716A and pertussis toxin, suggesting that theCB1 receptor and Gi/o protein mediated the regulation of AnNH levels. The observed increase in the levels of these lipids in SK-N-SH cells may be a mechanism for neuronal adaptation and may serve as a compensatory mechanism to counteract the continuous presence of EtOH. The present observation taken together with our previous results indicate the involvement of the endocannabinoid system in mediating some of the pharmacological actions of EtOH and may constitute part of a common brain pathway mediating reinforcement of drugs of abuse including EtOH.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1046/j.1471-4159.1999.0720522.x
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