CHARACTERIZATION OF 5-HYDROXYTRYPTAMINE 1A-LIKE BINDING-SITES IN HUMAN GANGLIONEUROBLASTOMA

Tumors derived from primitive neural crest cells are the most common malignant neoplasms of infancy and early childhood. We recently reported [H-3]8-hydroxy-2-(di-n-propylamino)tetralin specific binding in one such tumor, the ganglioneuroblastoma. We now characterize this binding and compare it with 5-hydroxytryptamine 1A (5-HT1A) sites in human and rat cortex. In competition studies, the rank order of drug affinities was suggestive of a 5-HT1A binding site: 5-HT > 8-OH-DPAT, RU24969 > methysergide, methiothepin, 1-2,5-dimethoxy-4-iodophenyl aminopropane (DOI), ketanserin > mianserin. Regression analysis showed a correlation with drug affinities in human cortex. [H-3]8-OH-DPAT binding was saturable and linear with absence of cooperativity, indicative of a single population of sites. The density of sites in ganglioneuroblastoma was two-to four-fold less than in human or rat cortex. [H-3]5-HT binding also identified 5-HT1 binding sites in ganglioneuroblastoma, comparable in density to [H-3]8-OH-DPAT-labelled sites. No specific binding was found using [H-3]paroxetine, [H-3]DOB, [H-3]ketanserin, or [H-3]mesulergine to label other types of 5-HT recognition sites. These data confirm the presence of a 5-HT1A-like binding site in human ganglioneuroblastoma.