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Comparison of the Pharmacological Characteristics of 2-[¹²⁵I]Iodomelatonin Binding Sites in the Lung, Spleen, Brain and Kidney of Chicken

1995; Karger Publishers; Volume: 4; Issue: 6 Linguagem: Inglês

10.1159/000109465

1424-8638

Celia S. Pang, Pak Lai Tang, Shiu Fun Pang, Gregory M. Brown,

Lanthanide and Transition Metal Complexes

We have compared the pharmacological characteristics of 2-[125I]iodo-melatonin binding to crude membrane preparations of the lung, spleen, brain and kidney of chicken. Saturation studies indicated significant differences (p < 0.05) in the equilibrium dissociation constant (Kd) and maximum number of binding site (Bmax) values among the four tissues studied. The descending order of affinities was lung = spleen > brain > kidney. Competition curves of 2-[125I]iodomelatonin binding to crude membrane preparations of all four chicken tissues by melatonin were studied simultaneously to reduce individual, physiological, age and interassay variations. Similar competition experiments were also performed on 2-phenylmelatonin, 2-iodomelatonin, 6-chloromelatonin, 6-hydroxymelatonin and N-acetylserotonin (NAS). Concentrations of indoles which inhibited 50% of specific 2-[125I]iodomelatonin binding (IC50) were calculated. The IC50 of 2-[125I]iodomelatonin inhibition curves by the indole compounds in different tissues showed the following descending orders of affinity: (1) melatonin: lung = spleen > brain > kidney, (2) 2-phenylmelatonin: lung = spleen = brain = kidney, (3) 2-iodomelatonin: lung = spleen = kidney > brain, (4) 6-chloromelatonin: lung = spleen = kidney > brain, (5) 6-hydroxymelatonin: kidney > lung = spleen = brain, and (6) NAS: kidney > lung = spleen > brain. The non-hydrolizable GTP analog, guanosine 5''-O-(3-thiotriphosphate) (GTPγS), exhibited differential effects on the saturable binding of the four tissues. GTPγS increased the Kd of 2-[125I]iodomelatonin binding by 2- to 3-fold in the lung and spleen, 0.5-fold in the brain and 1-fold in the kidney. Based on our findings, we would like to suggest that the 2-[125I]iodomelatonin binding sites in these four tissues may belong to three different high affinity (picomolar) subtypes of melatonin receptor. We name them cML1A represented by the lung and spleen, cML1B by the brain and cML1C by the kidney.