Selective conversion of β-endorphin into peptides related to γ- and α-endorphin
Selective conversion of β-endorphin into peptides related to γ- and α-endorphin
复制标题
β-内啡肽选择性转化为 γ- 和 α-内啡肽相关肽
作者：
J. Burbach;J. Loeber;J. Verhoef;V. Wiegant;E. R. Kloet;D. Wied
β-内啡肽（β-LPH61-91）是一种众所周知的内源性阿片配体。它和相关肽最近被认为与适应性行为的控制有关。在许多行为情况下，较小的β-内啡肽片段似乎比母体分子更活跃。它们的作用似乎与大脑中阿片受体的相互作用无关。此外，通过去除n端氨基酸消除γ-内啡肽（β-LPH61-77）的阿片样性质，得到比γ-内啡肽2,3具有更高行为活性的去酪氨酸-γ-内啡肽（β-LPH62-77, t -γ e）。在一些试验系统中，t γ e的中枢神经系统作用与抗精神病药物相似，α-内啡肽（β-LPH61-76）的作用与t γ e相反，在某些方面其活性与精神兴奋药物相当4。这种作用的对立表明γ型和α型内啡肽之间的平衡参与了脑功能的控制。我们在这里报道，无论是γ-内啡肽和t - γ-e，还是α-内啡肽和去酪氨酸-α-内啡肽（β-LPH62-769 dTαE），都可以由β-内啡肽通过与大脑突触体质膜富集部分相关的酶优先形成。这表明这些酶通过调节这些物质的产生在大脑稳态机制中起作用。
β-Endorphin (β-LPH61–91) is a well known endogenous opioid ligand. It and related peptides have recently been implicated in the control of adaptive behaviour. Smaller β-endorphin fragments appeared to be more active moieties than the parent molecule in a number of behavioural situations1. Their effects seemed to occur independently of interaction with opiate receptor sites in the brain. Moreover, elimination of the opiate-like properties of γ-endorphin (β-LPH61–77) by removing the N-terminal amino acid yielded des-tyrosine-γ-endorphin (β-LPH62–77, dTγE) which had greater behavioural activity than γ-endorphin2,3. The CNS effects of dTγE resembled those of neuroleptic drugs in several test systems, α-Endorphin (β-LPH61–76) exerted effects opposite to those of dTγE and in some aspects its activity was comparable to that of psychostimulant drugs4. This opposition of effects suggests that a balance between γ- and α-type endorphins is involved in the control of brain function5. We report here that either γ-endorphin and dTγE or α-endorphin and des-tyrosine-α-endorphin (β-LPH62–769 dTαE) can be formed preferentially from β-endorphin by enzymes associated with an enriched synaptosomal plasma membrane fraction from brain. It is suggested that these enzymes have a role in brain homeostatic mechanisms by regulating the generation of these substances.