Pang S F, Ayre E A, Poon A M, Pang C S, Yuan H, Wang Z P, Song Y, Brown G M
Clarke Institute of Psychiatry, Toronto, Ont., Canada.
Biol Signals. 1993 Jan-Feb;2(1):27-36. doi: 10.1159/000109475.
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.
研究了10微摩尔/升鸟苷5'-O-(3-硫代三磷酸)(GTPγS)（鸟苷5'-三磷酸的一种不可水解类似物）对2-[125I]碘褪黑素结合的影响。在鸡肺中，10微摩尔/升GTPγS显著增加（p<0.05）平衡解离常数（Kd）值，但不影响最大结合位点数（Bmax）。相反，在鸡脑中，GTPγS显著降低（p<0.05）Bmax，但不改变脑组织中2-[125I]碘褪黑素结合位点的Kd。在鸡肾中观察到第三种变化，GTPγS改变（p<0.05）2-[125I]碘褪黑素结合位点的Kd和Bmax。GTPγS对组织制剂中2-[125I]碘褪黑素结合产生不同影响的潜在原因尚不清楚。然而，我们推测它们可能代表具有不同受体-G-蛋白-效应器复合物的ML-1型褪黑素受体的不同亚型。以鸡肺中发现的2-[125I]碘褪黑素结合位点为代表的一组，其被GTPγS下调，导致Kd值增加，已被命名为ML-1α。第二组以脑2-[125I]碘褪黑素结合位点为例，其对GTPγS的反应是Bmax发生变化，已被标记为ML-1β。第三组的特征是GTPγS介导的Bmax和Kd均发生变化，在鸡肾中发现，已被称为ML-1γ。褪黑素受体的不同亚型可能解决同一物种内个体组织或相似组织但不同物种中报道的褪黑素不同生理作用的问题。根据与靶组织相关的ML-1受体的主要亚型，可以产生专门的反应。
