Gluten exorphin B5 stimulates prolactin secretion through opioid receptors located outside the blood-brain barrier
Gluten exorphin B5 stimulates prolactin secretion through opioid receptors located outside the blood-brain barrier
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DOI：
10.1016/j.lfs.2004.09.023
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发表时间：
2005-02-25
期刊：
影响因子：
6.1
通讯作者：
Delitala, G
中科院分区：
文献类型：
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作者：
Fanciulli, G;Dettori, A;Delitala, G
谷蛋白外啡肽B5（GE-B5）是在小麦面筋蛋白中发现的一种食物源性阿片肽。我们最近发现，GE-B5刺激大鼠催乳素（PRL）分泌，这种作用被预先给予阿片受体拮抗剂纳洛酮所消除。然而，由于纳洛酮的结构允许其穿过血脑屏障（BBB）并在中枢和外周拮抗阿片样物质的作用，因此无法根据这些数据确定GE-B5诱导的PRL释放是否通过位于BBB内部或外部的位点发挥作用。在这项研究中，我们试图确定GE-B5对PRL分泌的作用部位，通过用纳洛酮甲溴化物（NMB）预处理雄性大鼠，NMB是一种不穿过BBB的阿片类拮抗剂。对四组大鼠进行以下处理：1）静脉注射溶媒; 2）静脉注射GE-B5（3 mg/kg体重）; 3）腹膜内注射NMB（5 mg/kg体重），然后注射溶媒; 4）NMB，然后注射GE-B5。在溶媒或GE-B5给药后40分钟间隔采集用于PRL的血样。GE-B5刺激PRL分泌;在时间20时效果具有统计学显著性。NMB预处理完全消除PRL反应。我们的实验表明，GE-B5通过位于BBB外的阿片受体刺激PRL分泌。由于阿片肽不直接对PRL分泌产生影响，而是通过降低多巴胺能张力，因此我们的数据表明GE-B5可以在不穿过BBB的情况下改变脑神经递质的释放。(C)2004爱思唯尔公司All rights reserved.
Gluten exorphin B5 (GE-B5) is a food-derived opioid peptide identified in digests of wheat gluten. We have recently shown that GE-B5 stimulates prolactin (PRL) secretion in rats; this effect is abolished by preadministration of the opioid receptor antagonist naloxone. However, since the structure of naloxone allows it to cross the blood-brain barrier (BBB) and antagonize opioid effects centrally as well as peripherally, it could not established, on the basis of those data, if GE-B5-induced PRL release is exerted through sites located inside or outside the BBB. In this study, we sought to determine the site of action of GE-B5 on PRL secretion, by pretreating male rats with naloxone methobromide (NMB), an opioid antagonist that does not cross the BBB. Four groups of rats were given the following treatments: 1) intravenous vehicle; 2) intravenous GE-B5 (3 mg kg(-1) body weight); 3) intraperitoneal NMB (5 mg kg(-1) body weight), followed by vehicle; 4) NMB, followed by GE-B5. Blood samples for PRL were taken at intervals for 40 minutes after vehicle or GE-B5 administration. GE-B5 stimulated PRL secretion; the effect was statistically significant at time 20. NMB preadministration completely abolished PRL response. Our experiment indicates that GE-B5 stimulates PRL secretion through opioid receptors located outside the BBB. Since opioid peptides do not exert their effect on PRL secretion directly, but via a reduced dopaminergic tone, our data suggest that GE-B5 can modify brain neurotransmitter release without crossing the BBB. (C) 2004 Elsevier Inc. All rights reserved.