New concept of spare receptors and effectors
New concept of spare receptors and effectors
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DOI：
10.1007/s00232-004-0729-0
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发表时间：
2005-01-01
影响因子：
2.4
通讯作者：
Miyazaki, H
中科院分区：
文献类型：
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作者：
Marunaka, Y;Niisato, N;Miyazaki, H
本研究提出了备用受体的新概念。模型[A]：1)多个受体与一个效应器相连；2)如果激动剂占据了与一个效应器相连的其中一个受体，则效应器完全发挥作用。当与一个效应器相连的受体数目为“m”时，功能效应器(E)与激动剂浓度([α])之间的关系为：E=R-t/m(1-(1-1/1+K-d/[α])(M))(I)其中R-t为受体总数，K-d为激动剂与受体的解离常数。模型[B]：1)多个受体与一个效应器相连；2)只有当激动剂占据与一个效应器相连的所有受体时，效应器才起作用。E和[α]之间的关系如下：E=R-t/m(1-(1-1/1-K-d/[α])(M))(Ii)当m=1时，方程(I)和(Ii)与Michaelis-Menten方程完全相同。如果m大于1，则效应器效率的表观饱和度在模型[A]中变大，在模型[B]中变小。在这两个模型中，效应器的分数效率从激动剂与受体的分数结合中的解离程度随着TO的增大而变得更大。进一步，我们提出了一个变量模型，在效应器的功能构象变化中包含了激动剂占用依赖稳定性的概念；只有当与一个效应器相连的j个以上的受体被激动剂占据时，效应器才起作用(模型[M])。E与[α]的关系如下：E-M>；J=R-t/m(1-(J)Sigma(i=0)(m！/(m-j)！j！(1-1/1+K-d/[Alpha])((m-j))(1/1+K-d/[Alpha])(J))(Iii)
The present study provides a new concept of the spare receptor. Model [A]: 1) Several receptors connect with an effector; 2) if an agonist occupies one of the receptors connecting with one effector, the effector fully functions. When the number of receptors connecting with one effector is "m", the relationship between the functional effectors (E) and the concentration of agonists ([alpha]) is as follows:E = R-t / m (1 - (1 - 1/1+K-d/[alpha])(m)) (I)where R-t is the total number of receptors and K-d is the agonist dissociation constant from the receptor. Model [B]: 1) Several receptors connect with an effector; 2) only when agonists occupy all of the receptors connecting with one effector, the effector functions. The relationship between E and [alpha] is as follows:E = R-t / m (1 - (1-1 / 1-K-d / [alpha])(m)) (II)If m=1, equations (I) and (II) are exactly the same as the Michaelis-Menten equation. If m is larger than 1, the apparent saturation in the effector efficiency becomes larger in Model[A], and smaller in Model [B], respectively. The dissociation of the fractional efficiency of effectors from the fractional binding of agonists to receptors becomes larger as to becomes larger in both models. Further, we propose a variable model, including the concept of agonist-occupancy-dependent stability in the functional conformation change of the effector; only when more than j pieces of receptors connecting with one effector are occupied by agonists, the effector functions (Model [M]). The relationship between E and [alpha] is as follows:E-M > J = R-t/m(1-(j)Sigma(i=0)(m! / (m-j)!j!(1-1 / 1+K-d / [alpha])((m-j))(1 / 1+K-d / [alpha])(j))) (III)