Premium
Chronic Ethanol Increases the Cannabinoid Receptor Agonist Anandamide and Its Precursor N ‐Arachidonoylphosphatidylethanolamine in SK ‐ N ‐ SH Cells
Author(s) -
Basavarajappa Balapal S,
Hungund Basalingappa L
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0720522.x
Subject(s) - anandamide , veratridine , chemistry , cannabinoid receptor , cannabinoid , arachidonic acid , agonist , incubation , ethanol , receptor , endocannabinoid system , endocrinology , medicine , biochemistry , sodium , biology , sodium channel , enzyme , organic chemistry
: 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 precursor N ‐arachidonoylphosphatidylethanolamine (N‐ArPE) in SK‐N‐SH cells thatwere prelabeled with [ 3 H]arachidonic acid. The results indicatethat exposure of SK‐N‐SH cells to EtOH (100 m M ) for 72 hsignificantly increased levels of [ 3 H]AnNH and[ 3 H]N‐ArPE ( p < 0.05) (1.43‐fold for[ 3 H]AnNH and 1.65‐fold for [ 3 H]N‐ArPE). Exposure ofSK‐N‐SH cells to EtOH (100 m M , 24h) inhibited initially the formationof [ 3 H]AnNH at 24 h, followed by a progressive increase, reaching astatistical significance level at 72 h ( p < 0.05).[ 3 H]N‐ArPE increased gradually to a statistically significant levelafter 48 and 72 h ( p < 0.05). Incubation with exogenousethanolamine (7 m M ) and EtOH (100 m M , 72 h) did not resultin an additive increase in the formation of [ 3 H]AnNH. The formationof [ 3 H]AnNH and [ 3 H]N‐ArPE by EtOH was enhanced by theCa 2+ ionophore A23187 or by the depolarizing agent veratridine andthe K + channel blocker 4‐aminopyridine. Further, the EtOH‐inducedformation of [ 3 H]AnNH and [ 3 H]N‐ArPE was inhibited byexogenous AnNH, whereas only [ 3 H]AnNH formation was inhibited bythe CB1 receptor antagonist SR141716A and pertussis toxin, suggesting that theCB1 receptor and G i/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.