Abstract
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 ([a]) is as follows: where Rt is the total number of receptors and Kd 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 [a] is as follows: 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 m 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 [a] is as follows:
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Acknowledgmenets
This work was supported by a Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan (15659052, 15790120) and from the Japan Society of The Promotion of Science (15590189), a Grant-in-Aid from The Salt Science Research Foundation (0241), a Grant-in-Aid for Child Health and Development (14C-6) and a Research Grant for Nervous and Mental Disorders (15A-4) from the Ministry of Health, Labour and Welfare, Japan, and a Leading Project for Biosimulation from the Ministry of Education, Culture, Sports, Science and Technology, Japan.