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Comparative pharmacological studies of melatonin receptors: mt1, mt2 and mt3/qr2. tissue distribution of mt3/qr2 11Abbreviations: MCA-NAT, methoxy-carbonylamino-N-acetyltrypta- mine, 2-[125I]-I-MCA-NAT, 2-[125I]-iodomethoxy-carbonylamino-N-acetyltryptamine; 2-IbMT, 2-iodo-N-butanoyl-5-methoxytryptamine; 4-P-PDOT, 4-phenyl-2-propionamido-tetraline; DH97, N-pentanoyl-2-benzyltryptamine; S20760, 5-methoxy-N-cyclopropanoyl-tryptamine; S24635, N-[2-(5-carbamoylbenzofuran-3-yl)ethyl]-acetamide; S25726, N-methyl-(3-{2-[(cyclopropylcarbonyl)-amino]ethyl}benzo[b]furan-5-yl)carbamate; S26553, N-methyl-{1-[2-(acetylamino)ethyl]-naphthalen-7-yl}carbamate
- Source :
- Biochemical Pharmacology. 61:1369-1379
- Publication Year :
- 2001
- Publisher :
- Elsevier BV, 2001.
-
Abstract
- 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 1.6.99.2). 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.
Details
- ISSN :
- 00062952
- Volume :
- 61
- Database :
- OpenAIRE
- Journal :
- Biochemical Pharmacology
- Accession number :
- edsair.doi...........22bcbe5bce9434c40d4069e2f70bdcc5
- Full Text :
- https://doi.org/10.1016/s0006-2952(01)00615-3