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  • Title: Effects of guanosine 5'-O-(3-thiotriphosphate) on 2-[125I]iodomelatonin binding in the chicken lung, brain and kidney: hypothesis of different subtypes of high affinity melatonin receptors.
    Author: Pang SF, Ayre EA, Poon AM, Pang CS, Yuan H, Wang ZP, Song Y, Brown GM.
    Journal: Biol Signals; 1993; 2(1):27-36. PubMed ID: 8394768.
    Abstract:
    Effects of 10 mumol/l guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), a non-hydrolyzable analog of guanosine 5'-triphosphate, on 2-[125I]iodomelatonin binding were investigated. In the chicken lung, 10 mumol/l GTP gamma S significantly increased (p < 0.05) the equilibrium dissociation constant (Kd) values, but did not affect the maximum number of binding sites (Bmax). Conversely, in the chicken brain, GTP gamma S significantly depressed (p < 0.05) the Bmax, but did not change the Kd of the 2-[125I]iodomelatonin binding sites in the brain tissue. A third variation was observed in the chicken kidney with GTP gamma S altering (p < 0.05) both the Kd and the Bmax of 2-[125I]iodomelatonin binding sites. The reason underlying the different effects of GTP gamma S on 2-[125I]iodomelatonin binding in the tissue preparations is not clear. However, we would like to hypothesize that they may represent distinct subtypes of the ML-1-type melatonin receptor with different receptor-G-proteins-effector complex. The group represented by the 2-[125I]iodomelatonin binding sites found in the chicken lung, which is downregulated by GTP gamma S with a consequent increase in the Kd value, has been designated ML-1 alpha. The second group, exemplified by the brain 2-[125I]iodomelatonin binding sites, which respond to GTP gamma S with a change in Bmax, has been labelled ML-1 beta. The third group, characterized by GTP gamma S-mediated alterations in both Bmax and Kd and found in the chicken kidney, has been called ML-1 gamma. Different subtypes of melatonin receptors may address the issue of the different physiological actions of melatonin reported in individual tissues within the same species or similar tissues but different species. Specialized responses could be generated depending on the predominant subtype of ML-1 receptors associated with the target tissue.
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