Functional aspects of endorphins.

Radioimmunoassay of methionine-enkephalin, leucine-enkephalin and beta-endorphin were used in order to study the distribution and release of endorphins. The distribution pattern of enkephalin immunoreactivity in brain, including human brain, is quite different from that of beta-endorphin immunoreactivity. Separation of beta-endorphin and beta-lipotropin by column chromatography revealed that the contribution of beta-lipotropin to beta-endorphin immunoreactivity in brain is very small. In the anterior lobe of the pituitary both beta-endorphin and beta-lipotropin were found, whereas in the intermediate/posterior lobe almost all immunoreactivity was due to beta-endorphin; considerable amounts of enkephalin were also detected. Raising the concentration of potassium ions stimulated the release of met- and leu-enkephalin from striatal slices and the release of beta-endorphin immunoreactive material(s) from hypothalamic slices; both phenomena were dependent upon the presence of calcium ions. Studies of the release of beta-endorphin from isolated rat pituitaries revealed characteristic differences between the anterior and intermediate/posterior lobes; e.g., lysine vasopressin and extracts from the median eminence were highly effective in releasing beta-endorphin from the anterior lobe without affecting the release from the intermediate/posterior lobe; on the other hand, dopamine inhibited beta-endorphin release from the intermediate/posterior lobe without affecting release from the anterior lobe. Increased beta-endorphin levels were found after various stress conditions in rat plasma, as well as after treatment with metyrapone and vasopressin. In normal human plasma significant amounts of beta-endorphin were detected; increased levels were found in Addison's, Nelson's and Cushing's disease. Chronic opiate treatment of rats for 10 days did not affect brain levels of enkephalin or the beta-endorphin content of the hypothalamus, pituitary and plasma. Precipitated withdrawal decreased beta-endorphin in the anterior lobe and hypothalamus and increased beta-endorphin levels in the plasma. Long-term morphine treatment (30 days) decreased enkephalin and beta-endorphin content in some brain areas and in the intermediate/posterior pituitary lobe but not in the anterior lobe.