Secretory patterns of tryptophan metabolites in midgut carcinoid tumor cells.
Hormonal overproduction is a significant problem in patients with disseminated midgut carcinoid tumors. Serotonin (5-HT) is one major product secreted from such tumors and the urinary excretion of its metabolite (5-hydroxyindoleacetic acid, 5-HIAA) serves as an important tumor marker. The present study aimed at elucidating mechanisms of tryptophan metabolite secretion to facilitate the treatment of the carcinoid syndrome. When midgut carcinoid tumors were studied in primary cell cultures, several similarities with adrenergic neurons could be demonstrated. A marked dose-dependent depletion of intracellular 5-HT could be induced by reserpine, and monoamine oxidase-activity was revealed both in functional studies and by immunocytochemistry. Differences between tumors in the ratios of tryptophan metabolites released indicated that enzymes for synthesis and degradation of 5-HT were individually expressed. Treatment with the somatostatin analogue octreotide or with dexamethasone decreased the extracellular levels of tryptophan metabolites, but the mechanisms were partly different. In some tumors octreotide also decreased the synthesis of 5-HT, while dexamethasone markedly increased the intracellular 5-HIAA levels. It is of clinical interest to further elucidate these mechanisms, since the two drugs may have complementary actions in carotid crisis reactions.
Westberg
G
G
Department of Surgery, Sahlgrenska University Hospital, Göteborg, Sweden.
Ahlman
H
H
Nilsson
O
O
Illerskog
A
A
Wängberg
B
B
D006916:5-Hydroxytryptophan / Q000378:metabolism; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D002276:Carcinoid Tumor / Q000201:enzymology / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007414:Intestinal Neoplasms / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism; D015282:Octreotide / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018759:Adrenergic Uptake Inhibitors; D018931:Antineoplastic Agents, Hormonal; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D003907:Dexamethasone; D012110:Reserpine; D014364:Tryptophan; D006916:5-Hydroxytryptophan; D008995:Monoamine Oxidase; D015282:Octreotide