Studies on Adrenorphin in Pheochromocytoma*

Abstract
We studied the secretion and tissue contents of adrenorphin in human pheochromocytomas. In 17 human pheo-chromocytomas from 11 patients, we found a remarkably wide distribution in immunoreactive adrenorphin levels (3–7771 pg/mg tissue). Adrenormedullary pheochromocytomas contained a significantly larger amount of immunoreactive adrenorphin (2295 ± 1092 pg/mg, mean ± se) than did extramedullary ones (17.8 ± 8.4 pg/mg). Gel chromatographic studies revealed that immunoreactive adrenorphin consisted largely of material emerging at the position of synthetic adrenorphin in both phe-ochromocytoma and normal adrenal medulla tissue. Nicotine (10−5m) significantly stimulated the secretion of immunoreac-tive adrenorphin as well as catecholamines from cultured human pheochromocytoma cells. Adrenorphin was a more potent inhibitor of catecholamine secretion evoked by 10−5m nicotine than was met-enkephalin in cultured human pheochromocytoma 6 cells. The 50% inhibitory concentrations (IC50) were 1.1 × 10−6 and 6.5 × 10−5m for adrenorphin and met-enkephalin, respectively. The effect of adrenorphin was much the same as that of dynorphin-(1–13) (IC50) 1.0 × 10−6m) and BAM-12P (IC50, 4.5 × 10−6m). These results indicate the presence and secretion of adrenorphin in human pheochromocytomas. Adrenorphin may play an important role in regulating catecholamine secretion in human pheochromocytoma.