Cohen M L, Geary L E, Wiley K S
J Pharmacol Exp Ther. 1983 Feb;224(2):379-85.
Degradation of enkephalin by aminopeptidases has been established as an important functional mechanism that terminates the pharmacological action of enkephalins in the guinea-pig ileum. Aminopeptidases are a family of enzymes and little is known regarding the specificity of individual enzymes with respect to the degradation of enkephalins. Puromycin is a general inhibitor of aminopeptidases and bestatin is a more selective inhibitor of Leu-aminopeptidases and aminopeptidase B. Both agents are capable of inhibiting enkephalin degradation in broken cell preparations from brain. However, only bestatin enhanced the pharmacological response to enkephalin in the guinea-pig ileum and ileal longitudinal muscle. Bestatin enhanced the response to enkephalin in a concentration-dependent fashion. Furthermore, bestatin also decreased the formation of [3H]Tyr and increased [3H]Leu-enkephalin content after incubation of the guinea-pig ileum with [3H]Leu-enkephalin. In contrast, puromycin did not shift the concentration-response curve to Met-enkephalin in either the intact guinea-pig ileum or the ileal longitudinal muscle and, likewise, no alteration in the degradation of [3H]Leu- or Met-enkephalin occurred with puromycin. A small enhancing effect of puromycin on the duration of the inhibitory effect of enkephalin was observed only in the guinea-pig longitudinal muscle. This enhancement cannot be explained by an effect on enkephalin degradation, but may be related to some other action of puromycin. These data support the importance of aminopeptidase activity to the degradation of enkephalin and indicate that enzymes which have properties in common with Leu-aminopeptidases rather than arylamidases may be the primary aminopeptidases responsible for terminating the pharmacological actions of enkephalins in intact guinea-pig ileal preparations.
氨肽酶对脑啡肽的降解已被确认为一种重要的功能机制，它可终止脑啡肽在豚鼠回肠中的药理作用。氨肽酶是一类酶，关于个别酶对脑啡肽降解的特异性了解甚少。嘌呤霉素是氨肽酶的一种通用抑制剂，贝司他汀是亮氨酸氨肽酶和氨肽酶B的一种更具选择性的抑制剂。这两种药物都能够抑制来自脑的破碎细胞制剂中脑啡肽的降解。然而，只有贝司他汀增强了豚鼠回肠和回肠纵肌对脑啡肽的药理反应。贝司他汀以浓度依赖的方式增强了对脑啡肽的反应。此外，在用[³H]亮氨酸脑啡肽孵育豚鼠回肠后，贝司他汀还减少了[³H]酪氨酸的形成，并增加了[³H]亮氨酸脑啡肽的含量。相比之下，嘌呤霉素在完整的豚鼠回肠或回肠纵肌中均未使甲硫氨酸脑啡肽的浓度-反应曲线发生位移，同样，嘌呤霉素对[³H]亮氨酸或甲硫氨酸脑啡肽的降解也没有改变。仅在豚鼠纵肌中观察到嘌呤霉素对脑啡肽抑制作用持续时间有轻微的增强作用。这种增强不能用对脑啡肽降解的影响来解释，而可能与嘌呤霉素的其他某种作用有关。这些数据支持了氨肽酶活性对脑啡肽降解的重要性，并表明与亮氨酸氨肽酶而非芳基酰胺酶具有共同特性的酶可能是负责终止完整豚鼠回肠制剂中脑啡肽药理作用的主要氨肽酶。
