Identification and characterisation of 2-[¹²⁵I]iodomelatonin binding and mella 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 (K(d))=54 pM and maximal theoretical binding (B(max)) = 13 fmol/mg protein), and inhibited by guanosine-5'-o-(3-thiotriphosphate) (GTPγS) suggesting that these binding sites represent G protein-coupled melatonin receptors. REIT-PCR performed on mRNA isolated from the human fetal leptomeninges detected expression of the G protein-coupled melatonin receptor Mella, but not Mellb. In situ hybridisation confirmed the localisation of Mella mRNA transcripts over the leptomeninges of the fetal brain. The identification of 2- [¹²⁵I]iodomelatonin and Mella melatonin receptor expression in the fetal leptomeninges implies that melatonin may play a role in the early growth and development of the human brain.