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Degradation of beta-casomorphin in the rat brain in vivo.

The degradation of beta-casomorphin 1-5 (Tyr-Pro-Phe-Pro-Gly (beta CM]--an opiate-like acting pentapeptide--was investigated in brain stem and corpus striatum of male Wistar rats during the first 20 min after an intracerebroventricular (i.c.v.) application of 166 nmol [3H]Phe3-beta CM. Dependent on the time after [3H]Phe3-beta CM injection, the radioactivity carried by beta CM and its metabolites was estimated in the HCl-soluble tissue fraction of these brain structures. The separation of the intact pentapeptide from its metabolites was performed using HPLC-technique. In both brain regions a rapid decrease in the concentration of beta CM was observed during the first 10 min after [3H]Phe3-beta CM application (1st phase). 10 to 20 min after injection, the decrease in beta CM concentration was found to be considerably smaller (2nd phase). Moreover, beta CM is rapidly degraded forming phenylalanine and tyrosine as the main metabolites. Furthermore, at any time, small amounts of Phe-Pro-Gly, Phe-Pro, Pro-Phe-Pro-Gly and Tyr-Pro-Phe-Pro were estimated. From these results, the analgesic effect by i.c.v. application of 166 nmol beta CM is assumed to be caused rather by the intact pentapeptide molecule than by one of its metabolites.