Summary
Immunohistochemical studies for methionine- and leucine-enkephalin were performed on 26 phaeochromocytomas to elucidate the patho-physiological roles of enkephalins. Positive reactions were seen in all phaeochromocytomas with varying intensities. The location of methionine- and leucine-enkephalin agreed fairly well with each other. Stronger immunostaining was obtained in phaeochromocytomas secreting both adrenalin and noradrenalin than in those secreting predominantly noradrenalin. Paroxysmal hypertension was frequently observed in patients with adrenalin-secreting phaeochromocytomas, especially those with marked enkephalin positivity. Urinary excretion of metanephrine was significantly correlated with enkephalin positivity. These findings show that all phaeochromocytomas retain the ability to produce enkephalins of the adreno-medullary or extra-medullary chromaffin tissues from which they derive. Augmented enkephalin-immunoreactivity in adrenalin-producing phaeochromocytomas may be interpreted as reflecting a close association of enkephalins with adrenalin under physiological conditions.
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Baldi E, De Feo ML, Geppetti P, Carlà V, Maggi M, Pupilli C, Spillantini MG, Brocchi A, Mannelli M (1988) Measurement of catecholamines, met-enkephalin, somatostatin and substance P-like immunoreactivities in 12 human phaeochromocytomas. J Endocrinol Invest 11:133–138
Bostwick DG, Null WE, Holmes D, Weber R, Barchas JD, Bensch KG (1987) Expression of opioid peptides in tumors. N Engl J Med 317:1439–1443
Capella C, Riva C, Cornaggia M, Chiaravalli AM, Frigerio B, Solcia E (1988) Histopathology, cytology and cytochemistry of phaeochromocytomas and paragangliomas including chemodectomas. Path Res Pract 183:176–187
Clement-Jones V, Lowry PJ, Rees LH, Besser GM (1980) Metenkephalin circulates in human plasma. Nature 283:295–297
DeLellis RA, Blount M, Tischler AS, Wolfe HJ, Lee AK (1983) Leu-enkepahlin-like immunorectivity in proliferative lesions of the human adrenal medulla and extra-adrenal paraganglia. Am J Surg Pathol 7:29–37
Dupont A, Cusan L, Garon M, Alvarado-Urbina G, Labrie F (1977) Extremely rapid degradation of [3H] methionine-enkephalin by various rat tissuesin vivo andin vitro. Life Sci 21:907–914
Hacker GW, Bishop AE, Terenghi G, Varndell IM, Aghahowa J, Pollard K, Thurner J, Polak JM (1988) Multiple peptide production and presence of general neuroendocrine markers detected in 12 cases of human phaeochromocytoma and in mammalian adrenal glands. Virchows Arch [A] 412:399–411
Hambrook JM, Morgan BA, Rance MJ, Smith CFC (1976) Mode of deactivation of the enkephalins by rat and human plasma and rat brain homogenates. Nature 262:782–783
Hassoun J, Monges G, Giraud P, Henry JF, Charpin C, Payan H, Toga M (1984) Immunohistochemical study of phaeochromocytomas. An investigation of methionine-enkephalin, vasoactive intestinal peptide, somatostatin, corticotropin,β-endorphin, and calcitonin in 16 tumors. Am J Pathol 114:56–63
Hughes J, Smith TW, Kosterlitz HW, Fothergill LA, Morgan BA, Morris HR (1975) Identification of two related pentapeptides from the brain with potent opiate agonist activity. Nature 258:577–579
Imura H, Nakai Y, Nakao K, Oki S, Tanaka I, Jingami H, Yoshimasa T, Tsukada T, Ikeda Y, Suda M, Sakamoto M (1983) Biosythesis and distribution of opioid peptides. J Endocrinol Invest 6:139–149
Ito C (1989) Clinical significance of predominantly secreting catecholamines in phaeochromocytoma: adrenaline or noradrenaline. Tokyo Joshi Ikadaigaku Zasshi 59:397–408 (in Japanese)
Kilpatrick DL, Lewis RV, Stein S, Udenfriend S (1980) Release of enkephalins and enkephalin-containing polypeptides from perfused beef adrenal glands. Proc Natl Acad Sci USA 77:7473–7475
Kumakura K, Karoum F, Guidotti A, Costa E (1980) Modulation of nicotinic receptors by opiate receptor agonists in cultured adrenal chromaffin cells. Nature 283:489–492
Linnoila RI, Lack EE, Steinberg SM, Keiser HR (1988) Decreased expression of neuropeptides in malignant paragangliomas: an immunohistochemical study. Hum Pathol 19:41–50
Livett BG, Dean DM, Whelan LG, Udenfriend S, Rossier J (1981) Co-release of enkephalin and catecholamines from cultured adrenal chromaffm cells. Nature 289:317–319
Lloyd RV, Shapiro B, Sisson JC, Kalff V, Thompson NW, Beierwaltes WA (1984) An immunohistochemical study of phaeochromocytomas. Arch Pathol Lab Med 180:541–544
Lundberg JM, Hamberger B, Schultzberg M, Hökfelt T, Granberg P-O, Efendić S, Terenius L, Goldstein M, Luft R (1979) Enkephalin- and somatostatin-like immunoreactivities in human adrenal medulla and phaeochromocytoma. Proc Natl Acad Sci USA 76:4079–4083
Nakao K, Yoshimasa T, Suda M, Sakamoto M, Morii N, Ikeda Y, Matsukura S, Imura H (1984) Phaeochromocytoma and endogenous opioid peptides. Horumon To Rinsho 32:855–863 (in Japanese)
Osamura RY, Watanabe K, Yoshimasa T, Nakao K, Imura H (1984) Immunohistochemical localization of Met-enkephalin, Met-enkephalin-Arg6-Gly7-Leu8, Met-enkephalin-Arg6-Phe7 and Leu-enkephalin in human adrenal medulla and phaeochromocytomas. Peptides 5:993–1000
Parmer RJ, O'Connor DJ (1988) Enkephalins in human phaeochromocytomas: localization in immunoreactive, high molecular weight form to the soluble core of chromaffin granules. J Hypertens 6:187–198
Roisin MP, Artola A, Henry JP, Rossier J (1983) Enkephalins are associated with adrenergic granules in bovine adrenal medulla. Neuroscience 10:83–88
Sainai L, Guidotti A (1982) Opiate receptor-mediated inhibition of catecholamine release in primary cultures of bovine adrenal chromaffm cells. J Neurochem 39:1669–1676
Sullivan SN, Bloom SR, Polak JM (1978) Enkephalin in peripheral neuroendocrine tumours. Lancet I:986–987
Varndell IM, Tapia FJ, De Mey J, Rush RA, Bloom SR, Polak JM (1982) Electron immunocytochemical localization of enkephalin-like material in catecholamine-containing cells of the carotid body, the adrenal medulla, and in phaeochromocytomas of man and other mammals. J Histochem Cytochem 30:682–690
Viveros OH, Diliberto EJ Jr, Hazum E, Chang K-J (1979) Opiate-like materials in the adrenal medulla: evidence for storage and secretion with catecholamines. Mol Pharmacol 16:1101–1108
Wurtman RJ, Axelrod J (1966) Control of enzymatic synthesis of adrenaline in the adrenal medulla by adrenal cortical steroids. J Biol Chem 241:2301–2305
Yanase T, Nawata H, Kato K, Ibayashi H (1986) Catecholamines and opioid peptides in human phaeochromocytomas. Acta Endocrinol 113:378–384
Yoshimasa T, Nakao K, Li S, Ikeda Y, Suda M, Sakamoto M, Imura H (1983a) Plasma methionine-enkephalin and leucineenkephalin in normal subjects and patients with phaeochromocytoma. J Clin Endocrinol Metab 57:706–712
Yoshimasa T, Nakao K, Ikeda Y, Sakamoto M, Suda M, Imura H (1983b) Methionine-enkephalin, leucine-enkephalin, methionine-enkephalin-Arg6-Phe7 and methionine-enkephalin-Arg6-Gly7-Leu8 in human phaeochromocytoma. Life Sci 33:85–88
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This work is supported in part by a Grant-in-Aid from the Ministry of Education, Science and Culture (No. 61770949).
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Kodama, T., Ito, C., Fujimoto, Y. et al. Augmented enkephalin-immunoreactivity in adrenaline-producing phaeochromocytomas. Vichows Archiv A Pathol Anat 416, 417–422 (1990). https://doi.org/10.1007/BF01605147
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DOI: https://doi.org/10.1007/BF01605147