Metabolism of D-proline beta-casomorphin derivatives in the rat brain.
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.
Stark
H
H
Institute of Neurobiology and Brain Research, Academy of Sciences, Magdeburg, DDR.
Lössner
B
B
Matthies
H
H
Hartrodt
B
B
Born
I
I
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism; D002552:Cerebral Ventricles / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004723:Endorphins / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010446:Peptide Fragments; D051381:Rats; D011919:Rats, Inbred Strains
D004723:Endorphins; D010446:Peptide Fragments; C034812:beta-casomorphin 5; C059556:beta-casomorphin, des-Tyr-