Picomolar-affinity binding and inhibition of adenylate cyclase activity by melatonin in Syrian hamster hypothalamus.
1. The effect of melatonin on forskolin-stimulated adenylate cyclase activity was measured in homogenates of Syrian hamster hypothalamus. In addition, the saturation binding characteristics of the melatonin receptor ligand, [125I]iodomelatonin, was examined using an incubation temperature (30 degrees C) similar to that used in enzyme assays. 2. At concentrations ranging from 10 pM to 1 nM, melatonin caused a significant decrease in stimulated adenylate cyclase activity with a maximum inhibition of approximately 22%. 3. Binding experiments utilizing [125I]iodomelatonin in a range of approximately 5-80 pM indicated a single class of high-affinity sites: Kd = 55 +/- 9 pM, Bmax = 1.1 +/- 0.3 fmol/mg protein. 4. The ability of picomolar concentrations of melatonin to inhibit forskolin-stimulated adenylate cyclase activity suggests that this affect is mediated by picomolar-affinity receptor binding sites for this hormone in the hypothalamus.
Niles
L P
LP
McMaster University, Department of Biomedical Sciences, Hamilton, Ontario.
Hashemi
F
F
D015056:1-Methyl-3-isobutylxanthine / Q000037:antagonists & inhibitors; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001665:Binding Sites; D005576:Colforsin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006224:Cricetinae; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007457:Iodine Radioisotopes; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D008647:Mesocricetus; D011869:Radioligand Assay; D044094:Receptors, Melatonin; D017981:Receptors, Neurotransmitter / Q000187:drug effects*
D000067956:Adenylyl Cyclase Inhibitors; D007457:Iodine Radioisotopes; D044094:Receptors, Melatonin; D017981:Receptors, Neurotransmitter; D005576:Colforsin; D008550:Melatonin; D015056:1-Methyl-3-isobutylxanthine