kappa(1)-Opioid binding sites are the dominant opioid binding sites in surgical specimens of human pheochromocytomas and in a human pheochromocytoma (KAT45) cell line

The adrenal medulla produces opioids which exert paracrine effects on adren al cortical and chromaffin cells and on adrenal splanchnic nerves, via spec ific binding sites. The opioid binding sites in the adrenals are detectable mainly in the medullary part of it and differ in type between species. Thu s, the bovine adrenal medulla contains mostly kappa-opioid binding sites an d fewer delta- and mu-opioid binding sites while primate adrenals contain m ainly delta sites and few kappa-opioid binding sites. Most chromaffin cell tumors, the pheochromocytomas, produce opioids which suppress catecholamine production by the tumor. The aim of the present work was to identify the t ypes of opioid binding sites in human pheochromocytomas. For this purpose, we characterized the opioid binding sites on crude membrane fractions prepa red from 14 surgically excised pheohromocytomas and on whole KAT45 cells, a recently characterized human pheochromocytoma cell line. Our data showed t hat human pheohromocytomas are heterogeneous, as expected, with regard to t he production of catecholamines and the distribution and pro file of their opioid binding sites. Indeed, only one out of the 14 pheochromocytomas expr essed exclusively delta and mu opioid sites, while in the remaining 13 tumo rs kappa-type binding sites were dominant. The KAT45 cell line possessed a significant number of kappa(1) binding sites, fewer kappa(2)-opioid binding sites and kappa(3)-opioid binding sites, and minimal binding capacity for delta- and mu-opioid receptor agonists sites. More specifically, the kappa( 1) sites/cell were approximately 18,000, the kappa(2) 4500/cell and the kap pa(3) sites 2000/cell. Our findings for the surgical specimens and the cell line combined with previously published pharmacological data obtained from KAT45 cells suggest that kappa sites appear to be the most prevalent opioi d binding sites in pheochromocytomas. Finally, in normal bovine adrenals th e profile of opioid binding sites differs in adrenaline and noradrenaline p roducing chromaffin cells. To test the hypothesis that the type of catechol amine produced by a pheochromocytoma depends on its cell of origin, we comp ared our binding data with the catecholamine content of each pheochromocyto ma examined. We found no correlation between the type of the predominant ca techolamine produced and the opioid binding profile of each tumor suggestin g that this hypothesis may not be valid. (C) 1999 Elsevier Science B.V. All rights reserved.