Fig. 1: GPCRs induce both GTP binding and GTP release from Gα proteins and the process is agonist-mediated.
From: GTP release-selective agonists prolong opioid analgesic efficacy
a, Schematic of the proposed model, showing the conventional pathway of GDP-to-GTP exchange (left) and the expanded model to allow for both GTP and GDP release (right) as detailed in the linked Article14. A, agonist; R, receptor (asterisks indicate different active states); Ka, affinity constant; G protein; Gapo, unbound G protein (blue); GGDP, GDP-bound G protein (green); GGTP, GTP-bound G protein (red); α1 and α2, active state affinities. b, DAMGO-stimulated binding and release in CHO-MOR cells presented as raw data (in disintegrations per minute (dpm)) and the normalization to baseline and maximum response. c–g, Normalized binding and release with indicated agonists in CHO-K1 cells expressing MOR (c; n = 3 binding, 3 release), KOR (d; n =3 binding, 5 release), 5-HT1AR (e; n = 8 binding, 7 release), M2R (f; n = 3 binding, 3 release) and SST2R (g; n = 4 binding, 4 release). The raw data are presented in Extended Data Fig. 1. MPE, maximum possible effect. b–g, Data are mean ± s.e.m. and potency is presented as mean with 95% confidence interval. h, Comparison of potency in 35S-GTPγS binding versus release by unpaired, two-tailed t-test for each receptor comparing the individual potency (pEC50, where EC50 is half-maximal effective concentration) values measured per experiment. Data are mean with 95% confidence interval. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001; NS, not significant (P > 0.05).
