Discovery and characterization of [3H]8-OH-DPAT binding to HeLaS3 cells.
Some G protein-coupled receptors (GPCRs) have functional links to cancer biology, yet the manifestation of GPCRs in tumor types is little studied to date. Using a battery of radioligand binding assays, we sought to characterize GPCR recognition binding sites on HeLaS3 tumor cells. High levels of binding of the selective serotonin 5-HT(1A) receptor agonist [3H]8-OH-DPAT were observed in these cells. Saturation and homologous competition experiments indicated that [3H]8-OH-DPAT bound different populations of high- and low-affinity sites. In competition experiments, several serotonergic compounds displaced [3H]8-OH-DPAT binding with low potency from its high-affinity binding sites, suggesting that low-affinity binding is the predominant mode of binding. A variety of drugs targeting different classes of receptors did not affect [3H]8-OH-DPAT binding. These observations may help elucidate the pathophysiological and functional relevance of 5-HT receptors in tumor cells and link GPCRs and tumorigenic mechanisms to pharmacological and chemotherapeutic paradigms.
Feng
Jin-Jye
JJ
Institute of Molecular and Cellular Biology, National Tsing Hua University, 101 Section 2 Kuang-Fu Road, Hsinchu 30013, Taiwan, ROC. jin-jye.feng@mdsinc.com
Cheng
Fong-Chi
FC
Lin
Chun-Hsiung
CH
Wei
Jiann-Wu
JW
Yang
Shiaw-Der
SD
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D001667:Binding, Competitive; D004121:Dimethyl Sulfoxide / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D011869:Radioligand Assay; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D043562:Receptors, G-Protein-Coupled; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D004121:Dimethyl Sulfoxide