Melatonin exerts a variety of physiological activities that are mainly relayed through the MT1 and MT2 receptors. Low expressions of these receptors in tissues have led to widespread experimental use of the agonist 2-[125I]-iodomelatonin as a substitute for melatonin. We described three iodinated ligands: DIV880 & S70254 that are specific ligands at MT2 receptors, and SD6, an analogue of 2-[125I]-iodomelatonin with slightly different characteristics. Here we further characterized these new ligands, with regards to their molecular pharmacology. We performed binding experiments, saturation assays, association/dissociation rate measurements and autoradiography using sheep and rat tissues and recombinant cell lines. Our results showed that [125I]-S 70254 is selective for the MT2 receptor, and can be used with both cells and tissue. This radioligand can be used in autoradiography. Similarly, DIV880, a partial agonist (43% of melatonin on GTPγS binding assay) selective of MT2, can be used as a tool to selectively describe the pharmacology of this receptor in tissues samples. The molecular pharmacology of both hMT1 and hMT2, using a series of 24 ligands at these receptors and the new radioligands did not lead to noticeable variations in the profiles. For the first time, we described radiolabelled tools that are specific for one of the melatonin receptors (MT2). These tools are amenable to binding experiments and to autoradiography using sheep or rat tissues. These specific tools will permit to better understand the role and implication in physio-pathological processes of the melatonin receptors.
- The American Society for Pharmacology and Experimental Therapeutics