Source
Department of Neurology, George Washington University, Washington, DC 20010.
Abstract
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.