beta-Endorphin proteolysis by guinea-pig ileum myenteric plexus membranes: increased gamma-endorphin turnover after chronic exposure to morphine.

The influence of chronic morphine exposure in vitro on the biotransformation of beta-endorphin (beta E) was investigated using the myenteric plexus-longitudinal muscle of guinea-pig ileum. A membrane preparation was incubated with beta E and the degradation of beta E as well as the accumulation of several beta E fragments in the incubation medium were followed with time. The levels of peptides were determined by specific radioimmunoassays after separation by high-pressure liquid chromatography. It was found that exposure to morphine did not affect the disappearance of beta E, but altered the time course of accumulation of beta E fragments. In fact, the accumulation of gamma-endorphin, alpha-endorphin and des-tyrosine1-alpha-endorphin was enhanced, while that of des-tyrosine1-gamma-endorphin was not change. Additionally, the disappearance of gamma-endorphin appeared to be stimulated by morphine exposure. These data provide evidence that the fragmentation of beta E is changed by chronic morphine exposure in such a way that the turnover of gamma-endorphin is increased.