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Two melatonin receptors (MT 1 and MT 2 ) have been cloned. A third melatonin binding site, MT 3 , is known with remarkable and distinct pharmacological properties. We previously reported the purification of MT 3 and identified it as the enzyme dihydronicotinamide riboside:quinone reductase 2 (NQO2). To investigate the relationship between NQO2 and MT 3 , we generated a NQO2 À/À mouse strain. These mice no longer present MT 3 binding sites as measured with 2-[125 I]-iodo, 5-methoxycarbonylamino-N-acetyltryptamine, the specific MT 3 radioligand. These data establish NQO2 as part of the MT 3 binding sites in vivo and resolve the matter of the nature of the third melatonin binding site.

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