Identification and characterisation of 2-[125I]iodomelatonin binding and Mel1a melatonin receptor expression in the human fetal leptomeninges.
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.
Drew
J E
JE
Molecular Neuroendocrinology Group, Rowett Research Institute, Bucksburn, Aberdeen, UK. jed@rri.sari.ac.uk
Williams
L M
LM
Hannah
L T
LT
Barrett
P
P
Abramovich
D R
DR
Morgan
P J
PJ
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
D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; C044556:2-iodomelatonin; D008550:Melatonin