Ethanol alters the concentration of Met-enkephalin in brain by affecting peptide transport system-1 independent of preproenkephalin mRNA.
Alcohol-related events have been proposed to be under neurochemical control. For example, the concentration of methionine enkephalin (Met-enkephalin) in brain has been inversely correlated with ethanol consumption in alcohol-preferring and alcohol-nonpreferring mice. The concentrations of Met-enkephalin are controlled in part by peptide transport system-1 (PTS-1), a brain-to-blood transport system for Met-enkephalin located at the blood-brain barrier. We examined the relationships among concentrations of Met-enkephalin, preproenkephalin (PPE) mRNA, and PTS-1 activity in mice exposed to ethanol. PTS-1 activity decreased progressively during the process of addiction and then partially recovered within hours after withdrawal of ethanol. Serotonin lost its ability to modulate PTS-1 activity in exposed mice, indicating that regulation of PTS-1 activity was affected by ethanol. Concentrations of Met-enkephalin tended to move in the opposite direction from PTS-1 activity, increasing significantly with addiction. In naive mice, PPE mRNA levels correlated with the concentrations of Met-enkephalin. However, levels of PPE mRNA remained unchanged during addiction, withdrawal, and recovery, no longer correlating with concentrations of Met-enkephalin. These results suggest that ethanol affects concentrations of Met-enkephalin in brain through post-transcriptional mechanisms and that PTS-1 activity is one of those mechanisms.
Plotkin
S R
SR
Tulane Neuroscience Interdisciplinary Program, New Orleans, Louisiana, USA.
Banks
W A
WA
Waguespack
P J
PJ
Kastin
A J
AJ
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004744:Enkephalin, Methionine / Q000378:metabolism*; D004745:Enkephalins / Q000235:genetics; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009479:Neuropeptides / Q000378:metabolism*; D009994:Osmolar Concentration; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*
D004745:Enkephalins; D009479:Neuropeptides; D011498:Protein Precursors; D012333:RNA, Messenger; D000431:Ethanol; D004744:Enkephalin, Methionine; C033660:preproenkephalin