title: Identification and characterisation of 2-[125I]iodomelatonin binding and Mel1a melatonin receptor expression in the human fetal leptomeninges.
abstract: Melatonin binding sites were identified over the leptomeninges surrounding the human fetal brain using quantitative in vitro autoradiography and the melatonin agonist, 2-[125I]iodomelatonin. Binding was found to be saturable and of high affinity (dissociation constant (Kd) = 54 pM and maximal theoretical binding (Bmax) = 13 fmol/mg protein), and inhibited by guanosine-5'-o-(3-thiotriphosphate) (GTPgammaS) suggesting that these binding sites represent G protein-coupled melatonin receptors. RT-PCR performed on mRNA isolated from the human fetal leptomeninges detected expression of the G protein-coupled melatonin receptor Mel1a, but not Mel1b. In situ hybridisation confirmed the localisation of Mel1a mRNA transcripts over the leptomeninges of the fetal brain. 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.
authors.affiliation: Molecular Neuroendocrinology Group, Rowett Research Institute, Bucksburn, Aberdeen, UK. jed@rri.sari.ac.uk
authors.forename: J E
authors.initials: JE
authors.lastname: Drew
authors.forename: L M
authors.initials: LM
authors.lastname: Williams
authors.forename: L T
authors.initials: LT
authors.lastname: Hannah
authors.forename: P
authors.initials: P
authors.lastname: Barrett
authors.forename: D R
authors.initials: DR
authors.lastname: Abramovich
authors.forename: P J
authors.initials: PJ
authors.lastname: Morgan
mesh_terms: D005333:Fetus / Q000737:chemistry*; D015870:Gene Expression / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006801:Humans; D017403:In Situ Hybridization; D008550:Melatonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008578:Meninges / Q000737:chemistry* / Q000196:embryology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D044094:Receptors, Melatonin
chemical_list: D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; C044556:2-iodomelatonin; D008550:Melatonin