2-[125I]iodomelatonin-binding sites in the human kidney and the effect of guanosine 5'-O-(3-thiotriphosphate).
Putative melatonin receptors in normal kidney cortical tissues of patients with transitional cell carcinoma or renal cell carcinoma were characterized using a melatonin agonist, 2-[125I]iodomelatonin, as the radioligand. 2-[125I]Iodomelatonin-binding sites in the human kidney were stable, saturable, reversible, and of high affinity. The binding affinity was 15.2 +/- 2.5 pmol/L, and the binding density was 1.79 +/- 0.19 fmol/mg protein. The unity of the Hill coefficients and linearity of the Scatchard plots suggested that 2-[125I]iodomelatonin was bound to a single class of binding sites. Pharmacological characterization showed that these binding sites were highly specific to 2-iodomelatonin, melatonin, 6-hydroxymelatonin, and 6-chloromelatonin. Guanosine 5'-O-(3-thiotriphosphate) decreased the binding affinity and density of 2-[125I]iodomelatonin-binding sites in the kidney, suggesting that these binding sites are coupled to a G-protein. The characterization of 2-[125I]iodomelatonin-binding sites in normal kidney tissues taken from patients with transitional cell carcinoma or renal cell carcinoma suggests the existence of 2-[125I]iodomelatonin-binding sites in the human kidney cortex, which is in line with the findings of 2-[125I]iodomelatonin-binding sites in kidneys of other mammals and birds. The implication of a direct melatonin action on renal function in the human is proposed.
Song
Y
Y
Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
Tam
P C
PC
Poon
A M
AM
Brown
G M
GM
Pang
S F
SF
D000328:Adult; D000368:Aged; D001345:Autoradiography; D001665:Binding Sites; D002292:Carcinoma, Renal Cell / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000378:metabolism; D005260:Female; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology*; D006801:Humans; D007457:Iodine Radioisotopes; D007672:Kidney Cortex / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D008875:Middle Aged; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C044556:2-iodomelatonin; D008550:Melatonin