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Studies on Adrenorphin in Pheochromocytoma^*

Third Department of Internal Medicine, Faculty of Medicine, Kyushu University Fukoka 812
The Department of Biochemistry, Miyazaki Medical College Kiyotake, Miyazaki 889–16, Japan

Address requests for reprints to: Dr. Toshihiko Yanase, Third Department of Internal Medicine, Kyushu University, Fukuoka 812, Japan.

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^–5 M) 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^–5 M nicotine than was met-enkephalin in cultured human pheochromocytoma 6 cells. The 50% inhibitory concentrations (IC₅₀) were 1.1 x 10^–6 and 6.5 x 10^–5 M for adrenorphin and met-enkephalin, respectively. The effect of adrenorphin was much the same as that of dynorphin-(1–13) (IC50) 1.0 x 10^–6 M) and BAM-12P (IC₅₀, 4.5 x 10^–6 M).

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.

^* This work was supported in part by a Grant-in Aid for Special Project Research of Selected Intractable Neurological Disorders, Ministry of Education and a research grant from the Research Committee of Adrenal Hormone Disorders, Ministry of Health and Welfare, Japan.

Received July 15, 1986.