Comparative pharmacological studies of melatonin receptors: MT1, MT2 and MT3/QR2. Tissue distribution of MT3/QR2

Biochem Pharmacol. 2001 Jun 1;61(11):1369-79. doi: 10.1016/s0006-2952(01)00615-3.


The neurohormone melatonin is the central switch of the circadian rhythm and presumably exerts its activities through a series of receptors among which MT1 and MT2 have been widely studied. The third binding site of melatonin, MT3, has been recently characterized as a melatonin-sensitive form of the quinone reductase 2 (QR2, EC In the present work, we showed that the binding of melatonin at MT3/QR2 was better described with 2-[125I]-iodomethoxy-carbonylamino-N-acetyltryptamine (2-[125I]-I-MCA-NAT) and, most importantly, that it was measurable at 20 degrees while it has been initially described and thoroughly studied using 2-[125I]-iodomelatonin at 4 degrees. Under these novel conditions, binding to MT3 could be traced without cross-reactivity with MT1 and MT2 receptors and, moreover, under conditions similar to those used to measure MT3/QR2 catalytic activity. The pharmacology established here on hamster kidney samples using the reference compounds remained essentially as already described using other experimental conditions. A new series of compounds with nanomolar affinity for the MT3 binding site and a high MT3 selectivity versus MT1 and MT2 is reported. In addition, we further document the MT3/QR2 binding site by demonstrating that it was widely distributed among mammals, although inter-species and inter-tissues differences exist. The present report details new experimental conditions for the pharmacological study of melatonin-sensitive QR2 isoforms, and suggests that, in addition to an already demonstrated inter-species difference, inter-tissues differences in QR2 sensitivity to melatonin may exist in primates and, therefore, represent an original and interesting route of investigation on the effect of melatonin on MT3/QR2.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Binding, Competitive
  • Cells, Cultured
  • Cricetinae
  • Humans
  • Iodine Radioisotopes
  • Kinetics
  • Melatonin / analogs & derivatives
  • Melatonin / pharmacology
  • Mice
  • Rabbits
  • Radioligand Assay
  • Rats
  • Receptors, Cell Surface / antagonists & inhibitors
  • Receptors, Cell Surface / metabolism*
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Melatonin
  • Species Specificity
  • Temperature
  • Tissue Distribution
  • Tryptamines / pharmacology


  • Iodine Radioisotopes
  • N-pentanoyl-2-benzyltryptamine
  • Receptors, Cell Surface
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Melatonin
  • Tryptamines
  • 2-iodomelatonin
  • Melatonin