Preproenkephalin B-derived opioid peptides in human phaeochromocytomas.
We demonstrated the presence and the secretion in vivo and in vitro of immunoreactive preproenkephalin B-derived opioid peptides (alpha-neoendorphin, dynorphin and leumorphin) in human phaeochromocytomas. In seventeen human phaeochromocytomas and two human adrenal medullas, the tissue contents of immunoreactive preproenkephalin B-derived opioid peptides (alpha-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 immunoreactive alpha-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 alpha-neoendorphin and of dynorphin was observed. Nicotine (10(-5), 10(-4) mol/l) significantly stimulated the secretion of immunoreactive alpha-neoendorphin and dynorphin as well as leu-enkephalin 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 alpha-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.
D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000032:analysis / Q000378:metabolism*; D000328:Adult; D002478:Cells, Cultured; D004399:Dynorphins / Q000032:analysis / Q000378:metabolism*; D004723:Endorphins / Q000032:analysis / Q000378:metabolism*; D004745:Enkephalins / Q000032:analysis / Q000378:metabolism*; D004837:Epinephrine / Q000032:analysis; D005260:Female; D005934:Glucagon / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000494:pharmacology; D009638:Norepinephrine / Q000032:analysis; D010673:Pheochromocytoma / Q000032:analysis / Q000378:metabolism*; D011498:Protein Precursors / Q000032:analysis / Q000378:metabolism*; D011863:Radioimmunoassay
D004723:Endorphins; D004745:Enkephalins; D011498:Protein Precursors; C025681:alpha-neoendorphin; D009538:Nicotine; D004399:Dynorphins; D005934:Glucagon; C033660:preproenkephalin; D009638:Norepinephrine; D004837:Epinephrine