d-ala(2)-mephe(4)-met(0)-ol-enkephalin and Pheochromocytoma

The tissue contents of catecholamines (CAs) and methionine-enkephalin-like immunoreactivity (Met-enk) were examined in 8 patients with phaeochromocytomas (Phs). In 6, Ph cells were cultured, and the modes of secretion of CAs and Met-enk were examined. Tissue contents of CAs and Met-enk varied from patient to patient, but larger amounts of Met-enk were found in medullary Phs than extramedullary ones, regardless of the secreting CA type. Three patients with extramedullary Phs had clinically showed a sustained hypertension, whereas five with medullary Phs were normotensive or had occasional paroxysmal hypertension. Nicotine (10(-7) M to 10(-4) M) stimulated simultaneous secretion of CAs and Met-enk from the cultured human Ph cells. Met-enk, however, was not secreted in proportion to either epinephrine (E), norepinephrine (NE) or total CAs (E + NE). Met-enk, FK33-824 (FK) (Met-enkephalin analogue), and dynorphin 1-13 (Dyn) significantly suppressed the secretion of CA evoked by 10(-5) M nicotine. The 50% inhibitory concentrations (IC50) of Met-enk, FK, and Dyn were 5 X 10(-6) M, 9.9 X 10(-5) M, and 9.0 X 10(-8) M, respectively, in one patient and 9.0 X 10(-6) M, 1.5 X 10(-7) M, and 1.4 X 10(-7) M in another. In one patient, 10(-5) M naloxone inhibited the CA secretion evoked by 10(-5) M nicotine and did not reverse the 10(-5) M FK-induced suppression of CA secretion in the presence of 10(-5) M nicotine. These results suggest that human Phs may be heterogeneous with regard to storage and secretion of CAs and opioid peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Cells, Cultured; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Endorphins; Enkephalin, Methionine; Epinephrine; Female; Humans; Hypertension; Male; Middle Aged; Naloxone; Nicotine; Norepinephrine; Pheochromocytoma