Characterization of the monoamine uptake system in catecholamine storage vesicles isolated from a pheochromocytoma taken from a child.

The catecholamine storage vesicles of a pheochromocytoma taken from a child have been isolated and characterized. The tumor contained almost exclusively noradrenaline and a large proportion of this amine was vesicle-bound. The noradrenaline-containing vesicles showed great resemblance to bovine chromaffin granules. Their catecholamine and dopamine beta-hydroxylase contents were that of chromaffin granules; their morphology and density were similar to those of the subpopulation of these granules that contain noradrenaline. The pheochromocytoma vesicles contained in their membranes an abundant polypeptide of mol. wt 110,000, which was not apparent in bovine adrenal medulla vesicle membranes. Monoamine uptake by pheochromocytoma noradrenaline vesicles did not differ significantly from that observed in bovine chromaffin granules. The time-course, plateau level and KM for noradrenaline were similar for both types of organelles. Both had an oligomycin-resistant ATPase with similar properties. Investigations using the tetrabenazine derivative [2-3H]dihydrotetrabenazine (2-hydroxy-3-isobutyl-9,10-dimethoxy-1,2,3,4,6, 7-hexahydro-11b-H-benzo[a]quinolizine), which binds specially to the bovine chromaffin granule monoamine carrier indicated that granule membranes from the tumor have a 10-fold increased number of [2-3H]dihydrotetrabenazine binding sites, with no change in dissociation constant. As in the case of bovine chromaffin granules, [2-3H]dihydrotetrabenazine can be totally displaced by noradrenaline and serotonin. To account for the discrepancy observed between the uptake data (which indicated no difference with bovine chromaffin granules) and the [2-3H]dihydrotetrabenazine binding studies (which showed a large excess of binding sites in the tumor membranes), we propose that granules in the investigated tumor contained a large amount of inactive monoamine carrier.