The influence of gastric pentadecapeptide BPC 157 on acute and chronic ethanol administration in mice. The effect of N(G)-nitro-L-arginine methyl ester and L-arginine.
BACKGROUND
Alcohol disturbances, NO stimulation (by the NO-precursor L-arginine), and/or NO-synthesis blockade (by N(G)-nitro-L-arginine methyl ester, i.e. L-NAME) were challenged with stable gastric pentadecapeptide BPC 157, which inhibits both acute alcohol intoxication and alcohol withdrawal symptoms.


METHODS
Mice received intraperitoneally (i.p.) BPC 157 (10 microg/kg), L-NAME (10 mg/kg), and L-arginine (400 mg/kg), alone or in combination, 5 minutes before or after acute ethanol (4 g/kg i.p.) intoxication or after 0, 3, or 7 hours of withdrawal after drinking 20% alcohol for 13 days.


RESULTS
BPC 157 rapidly opposes the strongest disturbance presentations in acute intoxication (sustained ethanol anesthesia, complete loss of righting reflex, no reaction to external stimuli, hypothermia, 25% mortality) and withdrawal (prominent seizures). NO-agents: Aggravation of acute alcohol intoxication and opposition to withdrawal are common, but the later intervals affected by L-arginine and the action throughout the experiment by L-NAME are distinctive. Given together, L-arginine and L-NAME counteract each other, while either the "L-NAME presentation" (acute intoxication) or the "L-arginine presentation" (withdrawal) predominates. BPC157+NO-agent: In acute intoxication (L-NAME predominating in NO-system functioning to aggravate intoxication), both BPC157+L-NAME and BPC157+L-arginine follow the presentation of L-NAME, but without worsened mortality. In withdrawal (L-arginine predominating in NO-system functioning to oppose disturbance symptoms), BPC157+L-NAME follows the presentation of L-NAME, while BPC 157+L-arginine imitates that of L-arginine.


CONCLUSIONS
The relationships among pentadecapeptide BPC 157, the NO-system, acute alcohol intoxication, and opposed withdrawal may be important, presenting pentadecapeptide BPC 157 as a suitable alcohol antagonist.
Boban-Blagaic
Alenka
A
Department of Pharmacology, School of Medicine, University of Zagreb, Salata 11, POB 916, 10000 Zagreb, Croatia.
Blagaic
Vladimir
V
Romic
Zeljko
Z
Jelovac
Nikola
N
Dodig
Goran
G
Rucman
Rudolf
R
Petek
Marijan
M
Turkovic
Branko
B
Seiwerth
Sven
S
Sikiric
Predrag
P
D000428:Alcohol Drinking; D000818:Animals; D000897:Anti-Ulcer Agents / Q000378:metabolism*; D001120:Arginine / Q000378:metabolism*; D001519:Behavior / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*
D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D011506:Proteins; D000431:Ethanol; C083833:BPC 157; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester