Stark H, Lössner B, Matthies H, Hartrodt B, Born I
Institute of Neurobiology and Brain Research, Academy of Sciences, Magdeburg, DDR.
Biomed Biochim Acta. 1988;47(9):865-9.
The aim of the present study was to evaluate the metabolic breakdown of two biologically active derivatives of beta-casomorphin (beta CM)-i.e. D-proline4-beta CM (D-Pro4-beta CM) and des-tyrosine 1-D-proline4-beta CM (DT-D-Pro4-beta CM)- in the rat brain. After intracerebroventricular (icv.) administration of 0.78 nmoles of both [3H]D-Pro4-beta CM and [3H]DT-D-Pro4-beta CM, the concentration of the intact peptides and their metabolites was estimated in brain stem and corpus striatum. Both peptides were degraded in brain tissue forming a common metabolite. Phe-D-Pro-Gly. The metabolic half-lives of DT-D-Pro4-beta CM in brain stem and c. striatum were 22.6 min and 28.6 min, whereas those of D-Pro4-beta CM were 7.8 min and 8.2 min, respectively. According to both half-lives of the intact peptide and the kinetics of the formation of the stable metabolite Phe-D-Pro-Gly. DT-D-Pro4-beta CM seemed to be more resistant to biological degradation in brain tissue than D-Pro4-beta CM. In the case of D-Pro4-beta CM, the dipeptidylpeptidase IV (DP IV) (EC 3.4.14.-) is presumed to be the cardinal enzyme for the breakdown. Since the degradation of these peptides in brain tissue results in the unique metabolite Phe-D-Pro-Gly, the differences in the pattern of biological activities between D-Pro4-beta CM and DT-D-Pro4-beta CM may be due to the action of the corresponding intact peptide.
本研究的目的是评估大鼠脑中β-酪蛋白吗啡（βCM）的两种生物活性衍生物——即D-脯氨酸4-βCM（D-Pro4-βCM）和去酪氨酸1-D-脯氨酸4-βCM（DT-D-Pro4-βCM）的代谢分解情况。在脑室内（icv.）注射0.78纳摩尔的[3H]D-Pro4-βCM和[3H]DT-D-Pro4-βCM后，估计脑干和纹状体中完整肽及其代谢物的浓度。两种肽在脑组织中均发生降解，形成一种共同的代谢物苯丙氨酸-D-脯氨酸-甘氨酸。DT-D-Pro4-βCM在脑干和纹状体中的代谢半衰期分别为22.6分钟和28.6分钟，而D-Pro4-βCM的代谢半衰期分别为7.8分钟和8.2分钟。根据完整肽的半衰期以及稳定代谢物苯丙氨酸-D-脯氨酸-甘氨酸形成的动力学，DT-D-Pro4-βCM在脑组织中似乎比D-Pro4-βCM对生物降解更具抗性。对于D-Pro4-βCM，二肽基肽酶IV（DP IV）（EC 3.4.14.-）被认为是分解的主要酶。由于这些肽在脑组织中的降解产生独特的代谢物苯丙氨酸-D-脯氨酸-甘氨酸，D-Pro4-βCM和DT-D-Pro4-βCM之间生物活性模式的差异可能归因于相应完整肽的作用。
