Met-enkephalin, leu-enkephalin and other opiate-like peptides in human pheochromocytoma tumors

Opiate-like peptides, as measured by radioreceptor assay, were present in 20 samples from 9 human pheochromocytoma tumors obtained at surgery. The variation in peptide content of these samples, found in apparently viable tissue, ranged from 6-fold less to 90-fold higher than the mean value in normal human adrenal medulla. Subcellular fractionation of one tumor homogenate indicated that a large fraction of the opiate-like peptides are stored with catecholamines in chromaffin vesicles. Further analysis of pheochromocytoma opioid peptides revealed the presence of cryptic opioid activity, uncovered by trypsin treatment, and of six well-defined opioid peptide peaks, separated by high performance liquid chromatography. Peaks of opioid activity with high performance liquid chromatography retention times identical to met- and leu-enkephalin account for 43% and 27% of the recovered opioid activity, respectively. The massive stores of opioid peptides present and secreted from pheochromocytoma tumors may be responsible for some of the pleiomorphic symptomatology frequently observed in this disease.