Disease relevance of MTNR1A

• To investigate the mechanism of action of melatonin, by RT-PCR analysis we were able to demonstrate the expression, in prostate cancer cells, of a mRNA coding for the membrane Mel1a melatonin receptor [1].

High impact information on MTNR1A

• A G protein-coupled receptor for the pineal hormone melatonin was recently cloned from mammals and designated the Mel1a melatonin receptor [2].
• To delineate domains of high affinity melatonin receptors that are essential for melatonin binding, we generated chimeras between the human Mel1a melatonin receptor and the melatonin-related orphan H9 receptor [3].
• Therefore, the approach proposed in the present work can be successfully used for the determination of 'drug action' at the level of the human Mel1a melatonin receptor and evaluation of the efficacy of new selective melatonin analogues [4].
• Challenge of HEK293 cells with 1 microM melatonin had no effect on forskolin stimulated cyclic AMP levels, whereas in HEK293 cells engineered to stably over-express the human Mel1a melatonin receptor (B(max) > 400 fmol/mg protein) melatonin dose-dependently inhibited stimulated cyclic AMP levels (IC50 7.7 pM) [5].
• PCR analysis of human-rodent somatic cell hybrids showed that the receptor gene (MTNR1A) maps to human chromosome 4q35 [6].

Biological context of MTNR1A

• Exon 1 and exon 2 of the ovine melatonin-related receptor encode a protein of 575 amino acids which is 73.8% homologous to the human melatonin-related receptor and shows 40.9% homology with the ovine Mel1a melatonin receptor [7].
• Mutagenesis of human Mel1a melatonin receptor expressed in yeast reveals domains important for receptor function [8].
• A yeast functional colorimetric assay was employed to test the effects of site-directed point mutations on the function of the human Mel1a melatonin receptor [8].
• The identification of 2-[125I]iodomelatonin and Mel1a melatonin receptor expression in the fetal leptomeninges implies that melatonin may play a role in the early growth and development of the human brain [9].

Associations of MTNR1A with chemical compounds

• Dissociation constants for competition of 11 partial agonists and antagonist for 2-[125I]-iodomelatonin binding were between 15.5 (luzindole, pKi: 7.7) to 362 (4-phenyl-2-chloroacetamidotetraline, pKi: 9.1) fold higher for the Mel1b than for the Mel1a melatonin receptor [10].

References