Possible Interaction: Ethanol and Tissue Plasminogen Activator

“ Tissue type plasminogen activator antigen levels rose from 5.3 (2.2) μg/l to a maximum of 10.8 (3.8) μg/l nine hours after dinner with alcohol (P<0.001).”

“Furthermore, other drugs of abuse such as methamphetamine, nicotine, and ethanol increase tPA expression and activity in the nucleus accumbens, and behavioral analyses of tPA-knockout mice revealed that the tPA/plasmin system plays a crucial role in the rewarding effects of methamphetamine and nicotine.”

“Similarly, an increase of labelled diacylglycerol and phosphatidic acid but not of phosphatidylethanol occurred in [3H]palmitic acid prelabelled nuclei stimulated with TPA in the presence of ethanol.”

“When cells prelabelled with [3H]palmitic acid were stimulated with TPA in the presence of ethanol , an increase of labelled diacylglycerol and phosphatidylethanol in the nuclei was observed.”

“… low alcohol (1 hr, 37 degrees C) followed by incubation in the absence of alcohol (6 hr) resulted in an approximately 5- ….02) and an approximately 2- to 3-fold (0.89 +/- 0.04 vs. 2.07 +/- 0.29) increase in t-PA and u-PA … dehydrogenase ratio), respectively.”

“ Ethanol also increased tPA protein expression and release, and inhibited DNMT activity with a corresponding decrease in DNA methylation levels of the tPA promoter.”

“It was found that ethanol increased tPA mRNA levels, an effect mimicked by an inhibitor of DNA methyltransferase (DNMT) activity.”

“Tissue plasminogen activator tPA ) is involved in modulating neuronal plasticity by degrading the extracellular matrix proteins including fibronectin and laminin and is up‐regulated by ethanol in vivo.”

“Collectively, these results indicate, for the first time, that activation of tPA is effective in enhancing the rewarding effects of ethanol.”

“ Ethanol treatment dose-dependently induced tPA enzymatic activity in the nucleus accumbens (NAc).”

“Here we show that tissue-plasminogen activator (tPA), a protease implicated in neuronal plasticity and seizures, is induced in the limbic system by chronic ethanol consumption, temporally coinciding with up-regulation of NMDA receptors.”

“These results indicate that tPA mediates the development of physical dependence on ethanol by regulating NR2B-containing NMDA receptors.”

“ Chronic ethanol consumption induced an increase of PAA and t-PA antigen and a decrease of PAI (urokinase-type PA [u-PAI]) and PI in the body and pyloric region (PI only in the pyloric region).”

“Ultrastructural studies revealed that TPA stimulated regeneration of gastric mucosa damaged by ET after 24 and 48 hours.”

“Here we show that tissue plasminogen activator (tPA), a protease implicated in neuronal plasticity and seizures, is induced in the limbic system by chronic ethanol consumption, temporally coinciding with upregulation of NMDA receptors.”

“These results indicate that tPA mediates the development of physical dependence on ethanol by regulating NR2B-containing NMDA receptors.”