Vol. 290, Issue 1, 334-340, July 1999

Characterization of 2-[¹²⁵I]Iodomelatonin Binding Sites in Syrian Hamster Peripheral Organs

Pascal Paul¹ , Chantal Lahaye, Philippe Delagrange, Jean-Paul Nicolas, Emmanuel Canet and Jean A. Boutin

Division de Pharmacologie Moléculaire et Cellulaire, Institut de Recherches Servier, Croissy-sur-Seine (P.P., C.L., J.-P.N., E.C., J.A.B.); and Institut de Recherches Internationales Servier, Courbevoie (P.D.), France

The neurohormone melatonin is a key agent in synchronizing the circadian rhythms. At least three types of binding sites have been described for melatonin: the G-coupled, seven-transmembrane domain receptors mt₁ and MT₂ and a putative binding site called MT₃. The latter has been described in hamster brain membranes, and its binding capacity is optimum at 4°C. We further characterized this binding site on other peripheral hamster tissues, including intestine, liver, kidney, lung, muscle, and heart. We found a high level of binding sites (>30 fmol/mg of protein) in intestine and kidney. Furthermore, we completed the existing pharmacological profile of this site, which can now be described as 2-iodomelatonin > 6-chloromelatonin > methy-isobutyl-amiloride > acridine orange > 5-methylcarbonylamino-N-acetyltryptamine > prazosin > N-acetylserotonin > melatonin. This profile was found in all the hamster organs tested that had a large number of binding sites, namely, brain, intestine, kidney and liver. Furthermore, when comparisons were possible, the MT₃ pharmacological characteristics were similar to those described in the literature for hamster brain and testis. This profile was compared to the pharmacology obtained on human cloned mt₁ and MT₂ receptors and proved to be completely different, as expected. We provide new evidence for an alternate melatonin binding site not only in hamster brain but also in some peripheral organs.