Metabolism of D-proline beta-casomorphin derivatives in the rat brain.

H Stark, B Lössner, H Matthies, B Hartrodt, I Born

Index: Biomed. Biochim. Acta 47(9) , 865-9, (1988)

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Abstract

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.