Preproenkephalin B-derived opioid peptides in human phaeochromocytomas

Abstract

Abstract. We demonstrated the presence and the secretion in vivo and in vitro of immunoreactive preproenkephalin B-derived opioid peptides (α-neoendorphin, dynorphin and leumorphin) in human phaeochromocytomas. In senventeen human phaeochromocytomas and two human adrenal medullas, the tissue contents of immunoreactive preproenkephalin B-derived opioid peptides (α-neoendorphin, dynorphin and leumorphin) and leu-enkephalin were studied by specific RIAs. Compared with a remarkable wide distribution in amounts of immunoreactive leu-enkephalin (1063 ± 437 pg/mg, mean ± se), small amounts of immunnoreactive α-neoendorphin (22.6 ± 6.4 pg/mg) and dynorphin (8.5 ± 1.2 pg/mg) were detected in all seventeen human phaeochromocytomas and the two human adrenal medullas. Leumorphin-like immunoreactivity was detected in only four tumours. Gel chromatographic studies revealed the presence of preproenkephalin B-derived peptides and their high molecular forms. A significant positive correlation between the tumour tissue contents of immunoreactive α-neoendorphin and of dynorphin was observed. Nicotine (10−5, 10−4 mol/l) significantly stimulated the secretion of immunoreactive α-neoendorphin and dynorphin as well as leuenkephalin and catecholamines from cultured human phaeochromocytoma cells. Administration of 1 mg of glucagon to a patient with medullary phaeochromocytoma induced a rapid increase in the plasma concentration of immunoreactive α-neoendorphin with a concomitant increase in plasma catecholamines. These results indicate the presence of preproenkephalin B-derived opioid peptides in human phaeochromocytomas and human adrenal medullas and their secretion in human phaeochromocytomas.