Possible autocrine enkephalin regulation of catecholamine release in human pheochromocytoma cells.
OBJECTIVE
Pheochromocytomas are catecholamine-secreting tumors that also synthesize and secrete several neuropeptides, including opioids. A negative regulation of catecholamine secretion by opioids has been postulated in chromaffin cells. However, results obtained so far are contradictory when referred to human pheochromocytomas. The aim of this study was to define the role of locally produced enkephalins on catecholamine release in human pheochromocytoma cells.


METHODS
Cells obtained from eleven human pheochromocytomas of different genetic origins were cultured for 5 days. Cultures were maintained under basal condition or under enkephalin, dexamethasone and naloxone alone or in combination with enkephalin or dexamethasone-stimulated conditions. Catecholamine and enkephalin levels in the culture medium were measured by HPLC-ED and RIA respectively.


RESULTS
Enkephalin induced a decrease in norepinephrine levels in all tumor cultures. Dexamethasone treatment, which increased enkephalin levels, also decreased catecholamine levels. On the other hand, the addition of naloxone to the cultures reverted to normal the inhibitory action exerted by enkephalin and dexamethasone treatments.


CONCLUSIONS
These results suggest the existence of an autocrine negative regulatory loop exerted by enkephalin on norepinephrine release in human pheochromocytoma cells.
Pellizzari
Eliana Herminia
EH
Centro de Investigaciones Endocrinológicas (CONICET), Hospital de Niños R. Gutiérrez, Gallo 1330 - C1425EFD, Ciudad Autónoma de Buenos Aires, Argentina.
Barontini
Marta
M
Figuerola
María de Lourdes
Mde L
Cigorraga
Selva Beatriz
SB
Levin
Gloria
G
D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000378:metabolism*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D019898:Autocrine Communication / Q000502:physiology*; D002395:Catecholamines / Q000378:metabolism*; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D003470:Culture Media; D003907:Dexamethasone / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000378:metabolism; D004745:Enkephalins / Q000502:physiology*; D005260:Female; D006801:Humans; D007202:Indicators and Reagents; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010673:Pheochromocytoma / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D002395:Catecholamines; D003470:Culture Media; D004745:Enkephalins; D007202:Indicators and Reagents; D009292:Narcotic Antagonists; D009270:Naloxone; D004744:Enkephalin, Methionine; D003907:Dexamethasone