Schulteis G, Weinberger S B, Martinez J L
Department of Psychology, University of California, Berkeley 94720.
Peptides. 1989 Sep-Oct;10(5):913-9. doi: 10.1016/0196-9781(89)90168-x.
To understand better how [Leu]enkephalin (LE) acts to modulate learning and memory in rats, the plasma uptake, disappearance, and metabolism of LE were investigated following its intraperitoneal administration. Concentrations of [3H]-LE and its radioactive metabolites were determined by thin layer chromatography in plasma samples withdrawn from rats at various times after injection of peptide. As measured in rats receiving an IP injection of a dose of LE (3 micrograms/kg) that impairs active avoidance conditioning, the LE was very rapidly metabolized, with greater than 95% of plasma [3H] in the form of metabolites by 1 min after injection. Despite this rapid metabolism, low but measurable quantities of intact LE were detectable in plasma at all sampling times. Consistent with a greater potency of D-Ala2-[D-Leu5]enkephalin (DADLE) than of LE in modulating avoidance conditioning, DADLE was less rapidly metabolized than was LE following its IP administration. The metabolism of DADLE and LE in vivo was more rapid than it was in plasma in vitro, suggesting a role for membrane bound enzymes in the metabolism of IP-administered enkephalins. The data demonstrate that, despite a rapid hydrolysis of LE in vivo, sufficient LE is present in plasma following IP administration of a behaviorally active dose to support a role of circulating intact LE in the modulation of avoidance conditioning.
为了更好地理解亮氨酸脑啡肽（LE）如何调节大鼠的学习和记忆，在腹腔注射LE后，研究了其血浆摄取、消失及代谢情况。在注射肽后不同时间从大鼠采集血浆样本，通过薄层层析法测定[³H] - LE及其放射性代谢物的浓度。在接受腹腔注射能损害主动回避条件反射的剂量的LE（3微克/千克）的大鼠中检测到，LE代谢非常迅速，注射后1分钟时血浆中[³H]的95%以上以代谢物形式存在。尽管代谢迅速，但在所有采样时间的血浆中均可检测到少量但可测量的完整LE。与D - Ala² - [D - Leu⁵]脑啡肽（DADLE）在调节回避条件反射方面比LE具有更强效力一致，腹腔注射后DADLE的代谢速度比LE慢。DADLE和LE在体内的代谢比在体外血浆中更快，这表明膜结合酶在腹腔注射脑啡肽的代谢中起作用。数据表明，尽管LE在体内迅速水解，但在腹腔注射具有行为活性剂量后，血浆中仍存在足够的LE，以支持循环中的完整LE在调节回避条件反射中的作用。
