G protein-coupled receptors activation

Heptahelical domains are protein modules found in all known G-protein coupled receptors, made up of seven transmembrane helices interconnected by three extra and three intracellular loops. For most G-protein coupled receptors activated by small ligands, the binding site is located in a cavity formed by transmembrane domains 3, 5, 6 and 7. 

Hoffmann C, Gaietta G, Bunemann M et al (2005) A FlAsH-based FRET approach to determine G protein—coupled receptor activation in living cells. Nat Methods 2 171-176... 

Hoffmann, C., Gaietta, G., Bunemann, M., Adams, S. R., Oberdorff-Maass, S., Behr, B., Vilardaga, J. P., Tsien, R. Y., Ellisman, M. H. and Lohse, M. J. (2005). A FlAsH-based FRET approach to determine G protein-coupled receptor activation in living cells. Nat. Methods 2, 171-6. 

Weiss WI, Kobilka BK Structural insights into a G protein-coupled receptor activation. Curr Opin Struct Biol 2008 18 734. 

Sadoshima, J., Qiu, Z., Morgan, J.P., and Izumo, S. 1995. Angiotensin II and other hypertrophic stimuli mediated by G protein-coupled receptors activate tyrosine kinase, mitogen-activated protein kinase, and 90-kD S6 kinase in cardiac myocytes The critical role of Ca2+-dependent signaling. Circ. Res. 76 1-15. 

PHARMACOLOGICAL THEORIES OF G PROTEIN-COUPLED RECEPTOR ACTIVATION AND INVERSE AGONISM... 

Trinquet, E. et al. 2006. D-myo-inositol 1-phosphate as a surrogate of D-myo-inositol 1,4,5-tris phosphate to monitor G protein-coupled receptor activation. Anal. Biochem. 358, 126-135. 

Barak, L.S. et al. 1997. A /3-arrestin/green fluorescent protein biosensor for detecting G protein-coupled receptor activation. J. Biol. Chem. 272, 27497-27500. 

Struthers M, Yu H, Oprian DD. G protein-coupled receptor activation analysis of a highly constrained, straitjacketed rhodopsin. Biochemistry 2000 39 7938-7942. 

Pardo, L. Campillo, M. Giraldo, J. (1997) The effect of the molecular mechanism of G protein-coupled receptor activation on the process of signal transduction. Eur. J. Pharmacol. 335, 73-87. 

Fig. 2 The bitter taste signal transduction cascade. Bitter taste receptors are G-protein-coupled receptors. Activation of TAS2Rs results in the activation of the heterotrimeric G-protein complex a-gustducin (a-gust), 3 or pi, and yl3. The Py-subunits activate phospholipase C P2, (PLCj52) resulting in the production of inositol 1,4,5-trisphosphate (/P3). The IP3-mediated increase of intracellular calcium activates transient receptor potential channel 5 (TRPM5)...

Zhang G, Contos JJ, Weiner JA, Fukushima N, Chun J (1999) Comparative analysis of three murine G-protein coupled receptors activated by sphingosine-1-phosphate. Gene 227 89—99... 

Inactive conformation of a G-Protein coupled receptor Active conformation of a G-Protein coupled receptor Retinol-binding protein... 

Figure 7 Schematic representation of the molecular equihbria involved in G protein-coupled receptor activation ( reproduced with permission from publishers and authors of Hibert M, et al. Sanz F, ed. Trends in QSAR and Molecular Modelling 94, Barcelona Prous Sciences, 1995).

Chemistry, mechanism, and effects Glucagon is the product of the A cells of the endocrine pancreas. Like insulin, glucagon is a peptide but unlike insulin, glucagon acts on G protein-coupled receptors. Activation of glucagon receptors, which are located in heart, smooth muscle, and liver, stimulates adenylyl cyclase and increases intracellular cAMP. This results in increases in the heart rate and the force of contraction, increased hepatic glycogenolysis and gluconeogenesis and relaxation of smooth muscle. The smooth muscle effect is particularly marked in the gut. 

Released neurotransmitter interacts with postsynaptic receptors (E) and, in the case of G protein-coupled receptors, activates second messenger systems (F). The action of 5-HT is terminated (G) either by diffusion of 5-HT away from the synapse, with subsequent metabolism, or by the 5-HT being taken back up by a 5-HT transporter into the presynaptic neuron (i.e., reuptake), where it can be stored or metabolized. 

Ahuja S, Smith SO (2009) Multiple switches in G protein-coupled receptor activation. Trends Pharmacol Sci 30 494—502... 

Ambrosio M, Zum A, Lohse MJ (2011) Sensing G protein-coupled receptor activation. Neuropharmacology 60 45-51... 

Ali H, J Ahamed, C Hernandez-Munain, JL Baron, MS Krangel, DD Patel. 2000. Chemokine production hy G protein-coupled receptor activation in a human mast cell line roles of extracellular signal-regulated kinase and NFAT. J Immunol 165 7215. 

Ferguson, S. S., Caron, M. G. (2004). Green fluorescent protein-tagged beta-arrestin translocation as a measure of G protein-coupled receptor activation. Methods in Molecular... 

Lohse, M. J., Nuber, S., Hoffmann, C. (2012). Fluorescence/bioluminescence resonance energy transfer techniques to study G-protein-coupled receptor activation and signahng. Pharmacological Reviews, 64(2), 299—336. 

Bidlack, J. M., ParkhiU, A. L. (2004). Assay of G protein-coupled receptor activation of G proteins in native cell membranes using [35SJGTP gamma S binding. Methods in Molecular Biology, 237, 135—143. 

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