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 [3H]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 greater than 8-OH-DPAT, RU24969 greater than methysergide, methiothepin, 1-2,5-dimethoxy-4-iodophenyl aminopropane (DOI), ketanserin greater than mianserin. Regression analysis showed a correlation with drug affinities in human cortex. [3H]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. [3H]5-HT binding also identified 5-HT1 binding sites in ganglioneuroblastoma, comparable in density to [3H]8-OH-DPAT-labelled sites. No specific binding was found using [3H]paroxetine, [3H]DOB, [3H]ketanserin, or [3H]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.