Figure 5.

Rise-and-fall to steady-state time course profile examples of GPCR signaling. (a) Intracellular Ca²⁺ mobilization via the GnRH₁ receptor stimulated by 100 nM GnRH in the presence of extracellular Ca²⁺, an example of the precursor depletion with response degradation to steady-state model (data from Fig. 1a, presence of extracellular Ca²⁺, of⁷⁰). (b) ERK1/2 phosphorylation via the LPA₁ receptor stimulated by 10 μM LPA (data from Fig. 4a of⁷⁶, fit to Eq. (4) with baseline fixed at 1.0) (c) PKC activation and (d) Rho activation by the AT₁ receptor in vascular smooth muscle cells stimulated by 100 nM AngII (data from Fig. 3a,b, respectively, of⁷⁷, fit to Eq. 8). Note in (b) the fitting procedure involved minimization of outlier contribution to the fit (“Robust regression”)⁷⁴, which precluded estimation of R² values. Fitted parameter values are given in the file “Curve fit results” in Supporting Material. Initial rate was calculated using the equation, $\mathrm{Initial}\mathrm{rate}=\mathrm{SSR}\times \left(D{k}_1-\left(D-1\right)k_2\right)$ (See Appendix 1.1). Data in (a) were also analyzed using the mechanism equation for precursor depletion and response degradation to steady-state (Eq. 17 in Methods). The fitted curve overlies that of the rise-and-fall to steady-state fit.