Radioligand binding to intact cells as a tool for extended drug screening in a representative physiological context

• Published in: Drug discovery today. Technologies Vol. 17; pp. 28 - 34
• Main Authors: Vauquelin, Georges, Van Liefde, Isabelle, Swinney, David C.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2015
• Subjects: Animals; Drug Evaluation, Preclinical; Humans; Ligands; Pharmaceutical Preparations - metabolism; Protein Binding; Proteins - metabolism; Radioligand Assay
• ISSN: 1740-6749; 1740-6749
• DOI: 10.1016/j.ddtec.2015.09.001

•Radioligand binding on intact cells offers advantages compared to membranes (M) and tissues (T).•Versatility of the assays and physiological relevance of binding data (M).•Detection of micro-pharmacokinetic manifestations like rebinding (M).•Access to homologous receptor populations and negative controls (T).•Straightforward comparison of binding and functional data on the same system (M, T). Radioligand binding assays on intact cells offer distinct advantages to those on membrane suspensions. Major pharmacological properties like drug affinity and binding kinetics are more physiologically relevant. Complex mechanisms can be studied with a wider choice of experimental approaches and so provide insights into induced-fit type binding, receptor internalisation and even into pharmacomicrokinetic phenomena like drug rebinding and partitioning into the membrane. Hence, intact cell binding constitutes a valuable addition to the pharmacologist's toolbox.