Boban-Blagaic Alenka, Blagaic Vladimir, Romic Zeljko, Jelovac Nikola, Dodig Goran, Rucman Rudolf, Petek Marijan, Turkovic Branko, Seiwerth Sven, Sikiric Predrag
Department of Pharmacology, School of Medicine, University of Zagreb, Salata 11, POB 916, 10000 Zagreb, Croatia.
Med Sci Monit. 2006 Jan;12(1):BR36-45. Epub 2005 Dec 19.
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.
MATERIAL/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.
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.
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.
酒精干扰、一氧化氮刺激（通过一氧化氮前体L-精氨酸）和/或一氧化氮合成阻断（通过N(G)-硝基-L-精氨酸甲酯，即L-NAME），用稳定的胃十五肽BPC 157进行挑战，该肽可抑制急性酒精中毒和酒精戒断症状。
材料/方法：小鼠在急性乙醇（4 g/kg腹腔注射）中毒前或中毒后5分钟，或在饮用20%酒精13天后戒断0、3或7小时后，单独或联合腹腔注射（i.p.）BPC 157（10微克/千克）、L-NAME（10毫克/千克）和L-精氨酸（400毫克/千克）。
BPC 157能迅速对抗急性中毒（持续乙醇麻醉、翻正反射完全丧失、对外界刺激无反应、体温过低、25%死亡率）和戒断（明显癫痫发作）中最强烈的干扰表现。一氧化氮试剂：急性酒精中毒加重和对戒断的对抗很常见，但L-精氨酸影响的后期间隔以及L-NAME在整个实验中的作用是独特的。L-精氨酸和L-NAME一起使用时相互抵消，而“L-NAME表现”（急性中毒）或“L-精氨酸表现”（戒断）占主导。BPC157 + 一氧化氮试剂：在急性中毒（L-NAME在一氧化氮系统功能中占主导以加重中毒）中，BPC157 + L-NAME和BPC157 + L-精氨酸均遵循L-NAME的表现，但死亡率未恶化。在戒断（L-精氨酸在一氧化氮系统功能中占主导以对抗干扰症状）中，BPC157 + L-NAME遵循L-NAME的表现，而BPC 157 + L-精氨酸模仿L-精氨酸的表现。
十五肽BPC 157、一氧化氮系统、急性酒精中毒和相反的戒断之间的关系可能很重要，表明十五肽BPC 157是一种合适的酒精拮抗剂。
