Abstract
In order to confirm the hypothesis that morphine analgesia is revealed by endogenous morphine-like factor which was released by morphine, the effect of morphine on the amount of met-enkephalin and tyr-gly-gly (TGG), one of the fragments of met-enkephalin, in the corpus striatum of rat was investigated using a high pressure liquid chromatography. Met5-enkephalin content was not changed by intraperitoneally injected 0.5 mg/kg morphine. However, TGG was significantly increased approximately 3 times by 0.5 mg./kg morphine and 1.8 times by 20 mg/kg morphine. The increase of TGG content by 0.5 mg/kg morphine was abolished by lesion of the dorsal periaqueductal central gray (PAG) in rats. A dose of 250 mg/kg D-phenylalanine, carboxypeptidase inhibitor, abolished the increase of TGG due to 20 mg/kg morphine administration.
These results indicate the possibilities that TGG in striatum was increased by activation of the pathway from the dorsal PAG to the striatum due to morphine. TGG was increased as a metabolite of met-enkephalin liberated by morphine and D-phenylalanine inhibit the metabolism of met-enkephalin.