Potential modulation of plasma ghrelin and glucagon-like peptide-1 by anorexigenic cannabinoid compounds, SR141716A (rimonabant) and oleoylethanolamide
Potential modulation of plasma ghrelin and glucagon-like peptide-1 by anorexigenic cannabinoid compounds, SR141716A (rimonabant) and oleoylethanolamide
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DOI：
10.1079/bjn20041256
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发表时间：
2004-11-01
影响因子：
3.6
通讯作者：
Lambert, DM
中科院分区：
文献类型：
--
作者：
Cani, PD;Montoya, ML;Lambert, DM
已知CB 1大麻素受体拮抗剂N-哌啶基-5-（4-氯苯基）-1-（2，4-二氯苯基）-4-甲基吡唑-3-甲酰胺（利莫那班; SR 141716 A）和油酰乙醇胺（OEA）通过至少部分地外周调节进食来减少摄食。在24 h禁食和进食大鼠中研究了全身SR 141716 A或OEA（5 mg/kg）给药对摄食量的影响。在禁食大鼠中，SR 141716 A和OEA对摄食量产生抑制，可在注射后前20分钟测量。在接受OEA的动物中消除了在溶剂注射大鼠中观察到的胃饥饿素水平增加，并在SR 141716 A中显著降低。给药后20 min，OEA和SR 141716 A均未改变胰高血糖素样肽-1（7-36）酰胺门静脉水平。在进食大鼠中，SR 141716 A和OEA给药大鼠的血浆胃饥饿素水平比溶剂注射大鼠低35%。这些结果表明大麻素剂对循环胃饥饿素水平的影响，并表明它们对食欲的短期作用似乎与胃肠道食欲肽分泌的控制一致，主要在胃肠道的上部表达。
The CB1 cannabinoid receptor antagonist, N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (rimonabant; SR141716A), and oleoylethanolamide (OEA) are known to reduce food consumption, by, at least partially, a peripheral regulation of feeding. The effects of systemic SR141716A or OEA (5 mg/kg) administrations on food consumption in 24 h food-deprived and fed rats were investigated. In fasted rats, SR141716A and OEA produced an inhibition in food intake measurable the first 20 min following injection. The increase in ghrelin levels observed in the vehicle-injected rats was abolished in animals receiving OEA and significantly reduced with SR141716A. Neither OEA nor SR141716A modified glucagon-like peptide-1 (7-36) amide portal levels 20 min after the administration. In fed rats, plasma ghrelin levels of SR141716A- and OEA-treated rats were 35 % lower as compared with those of the vehicle-injected rats. These results show an influence of cannabinoid agents on circulating ghrelin levels and suggest that their short-term action on appetite seems to be in accordance with the control of secretion of gastrointestinal orexigenic peptides, mainly expressed in the upper part of the gastrointestinal tract.