Organs from mice deleted for NRH:quinone oxidoreductase 2 are deprived of the melatonin binding site MT3

Abstract

Two melatonin receptors (MT₁ and MT₂) 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‐[¹²⁵I]‐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.