Organs from mice deleted for NRH:quinone oxidoreductase 2 are deprived of the melatonin binding site MT 3

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 −/− 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.