Figure 8.

Kinetic mechanistic model of agonism incorporating regulation of signaling. Both mechanisms of short-term signaling regulation are included – receptor desensitization (yellow) and response degradation (pink). The response generation process is in green. In this process, the response precursor ($E_P$) is converted to the response ($E$) by the agonist-occupied receptor ($\mathit{RA}$). This proceeds at a rate defined by $k_{\tau }$, the transduction rate constant, which is the initial rate of response generation by the agonist-occupied receptor. Receptor desensitization is represented by transformation of $\mathit{RA}$ into the inactive receptor $R_{0}A$ that does not generate a response (because it can’t couple to $E_P$). The rate constant for desensitization is $k_{\mathit{DES}}$. Degradation of response is represented by decay of $E$ to $D$, governed by the degradation rate constant k_D. This model is an extension the original kinetic mechanistic model³³, extended here to incorporate receptor desensitization.