Catecholamines and opioid peptides in human phaeochromocytomas

Abstract

The tissue contents of catecholamines (CAs) and methionineenkephalin-like immunoreactivity (Metenk) 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 nonmotensive or had occasional paroxysmal hypertension. Nicotine (10-7M to 10-4M) 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), norephineprine (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 .times. 10-6 M, 9.9 .times. 10-5 M, and 9.0 .times. 10-8 M, respectively, in one patient and 9.0 .times. 10-6 M, 1.5 .times. 10-7 M, and 1.4 .times. 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 heterogenous with regard to storage and secretion of CAs and opioid peptides. The differences in the tissue content of opioid peptides and the suppressive effect of opioid peptides on the CA secretion may play an important role in clinical manifestations such as hypertension.