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• W2000662088 abstract "Background: We demonstrated previously that striatal adenosine modulates ethanol‐induced motor incoordination (EIMI) via adenosine A 1 receptors coupled to pertussis toxin (PT)‐sensitive G protein and adenylyl cyclase‐cyclic adenosine monophosphate (cAMP). Additionally, intrastriatal (IST) PT antagonizes EIMI and its potentiation by the adenosine A 1 agonist N 6 ‐cyclohexyladenosine; it also inhibits cAMP concentration. Methods: Guide cannulas were stereotaxically implanted for IST pretreatment with PT followed 5 days later by IST of N 6 ‐cyclohexyladenosine and intraperitoneal ethanol. The adenosine diphosphate (ADP) ribosylation reaction involved PT‐catalyzed [ 32 P]nicotinamide adenine dinucleotide (NAD) labeling of rat striatal membranes. Antagonism of EIMI (Rotorod method) after IST microinfusion of PT was investigated to determine whether it was due to a decrease in the functional activity of G proteins due to ADP ribosylation of the G iα subunit caused it. Results: Striatal membranes from IST PT (0.5 μg)–treated animals exhibited significantly attenuated (up to 90%) in vitro ADP ribosylation with [ 32 P]NAD. Striatal membranes from animals injected with ethanol (1.5 g/kg intraperitoneally) exhibited statistically significant increase (11%) in in vitro ADP ribosylation. Similarly, ethanol (50 mM) added to striatal membranes from untreated animals produced significant stimulation of in vitro ADP ribosylation. The decrease in the functional activity of G proteins due to ADP ribosylation of the G iα subunit after IST PT was functionally correlated with marked attenuation in EIMI, as observed previously. This finding suggests a blockade of functional activity of PT‐sensitive striatal G i/ G o proteins (i.e., fewer available sites for labeled NAD incorporation). The in vivo ethanol results indicate that it must have caused an increase in the ribosylation capacity of G iα in vivo (i.e., increased G i activity). Increased ADP ribosylation by in vitro ethanol increases G i /G o activity, consistent with EIMI, as previously reported. Conclusions: The results provide biochemical evidence of an ethanol‐induced increase in ADP ribosylation of G iα causing a decrease in the functional activity of G proteins coupled via G i /G o to adenylyl cyclase‐cAMP. These results confirm the previously observed antagonism of EIMI by PT (IST)." @default.
• W2000662088 created "2016-06-24" @default.
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• W2000662088 date "2004-09-01" @default.
• W2000662088 modified "2023-10-09" @default.
• W2000662088 title "Acute Ethanol‐Induced Adenosine Diphosphate Ribosylation Regulates the Functional Activity of Rat Striatal Pertussis Toxin–Sensitive G Proteins" @default.
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• W2000662088 doi "https://doi.org/10.1097/01.alc.0000139817.53197.41" @default.
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