G-protein coupled receptor ligands

Figure 14-1. Signaling via G protein-coupled receptors. Ligand binding to its cell-surface receptor initiates interaction of the receptor with the heterotrimeric G protein for which it is specific. A conformational change in the G protein brought about by binding of the ligand-receptor complex promotes exchange of GDP for GTP. The activated Gd-GTP dissociates from the Gp complex and both can interact with effectors, which carry on the signal to the mechanism that implements the cellular response.

The antibiotic and G-protein coupled receptor ligand martinelline 199 (Scheme 12.28) is a quinoline alkaloid that was isolated from root extracts of Martindla iqui-tosensis [95]. 

Key Words Bradykinin chimerism galparan G protein-coupled receptor ligand binding mastoparan secretion vasopressin. 

HT receptors consist of at least 3 distinct types of molecular structures G protein-couples receptors, ligand-gated ion channels and transporters (Table 1) [62],... 

Grunbeck, A., Sakmar, T. P. (2013). Probing G protein-coupled receptor—Ligand interactions with targeted photoactivatable cross-hnkers. Biochemistry, 52(48), 8625—8632. http //dx.doi.Org/10.1021/bi401300y. 

Ward, R.J., Milligan, G. Stractural and biophysical characterization of G protein-coupled receptor ligand binding using resonance energy transfer and fiuorescent labelling techniques. Biochim. Biophys. Acta 1838, 3-14 (2014)... 

Lazareno, S., and Birdsall, N. J. M. (1995). Detection, quantitation, and verification of allosteric interactions of agents with labeled and unlabeled ligands at G protein-coupled receptors Interactions of strychnine and acetylcholine at muscarinic receptors. Mol. Pharmacol. 48 362-378. 

G-protein-coupled receptor kinases (GRKs) are a family of enzymes that catalyze the phosphorylation of threonine or serine residues on G-protein-coupled receptors. Characteristically, GRKs only phosphorylate the ligand-activated form of the receptors. Phosphorylation by GRKs usually leads to impaired receptor/G-protein coupling. 

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. 

A number of agonists can act through several receptor classes, e.g., ion channels and G-protein-coupled receptors. To set receptor subtypes permanently linked to ion channels ( ligand-gated ion channels) apart... 

For differentiation of G-protein-coupled receptor sub-types from subtypes permanently linked to ion channels (ligand-gated ion channels) the terms metabotropic versus ionotropic receptors, respectively, are used. Prime examples of metabotropic receptors are given by the lnGlu receptor family of G-protein-coupled glutamate receptors. 

G-protein-coupled receptors Bioinformatics NMR-Based Ligand Screening... 

Wise A, Jupe SC, Rees S (2004). The identification of ligands at orphan G-protein coupled receptors. Annu Rev Pharmacol Toxicol 44 43-66... 

Enterochromaffin cells are interspersed with mucosal cells mainly in the stomach and small intestine. In the blood, serotonin is present at high concentrations in platelets, which take up serotonin from the plasma by an active transport process. Serotonin is released on platelet activation. In the central nervous system, serotonin serves as a transmitter. The main serotonin-containing neurons are those clustered in form of the Raphe nuclei. Serotonin exerts its biological effects through the activation of specific receptors. Most of them are G-protein coupled receptors (GPCRs) and belong to the 5-HTr, 5-HT2-, 5-HT4-, 5-HTs-, 5-HT6-, 5-HT7-receptor subfamilies. The 5-HT3-receptor is a ligand-operated ion channel. 

Synaptic Transmission. Figure 1 Synaptic transmission. The presynaptic terminal contains voltage-dependent Na Superscript and Ca2+ channels, vesicles with a vesicular neurotransmitter transporter VNT, a plasmalemmal neurotransmitter transporter PNT, and a presynaptic G protein-coupled receptor GPCR with its G protein and its effector E the inset also shows the vesicular H+ pump. The postsynaptic cell contains two ligand-gated ion channels LGIC, one for Na+ and K+ and one for Cl-, a postsynaptic GPRC, and a PNT. In this synapse, released transmitter is inactivated by uptake into cells. 

Of the several classes of receptors for endogenous chemical signals [3], two are used as postsynaptic receptors in synaptic transmission ligand-gated ion channels (LGICs) and G protein-coupled receptors (GPCRs Fig. 1). Due to the large number of transmitters and the existence of several receptor types for almost all, postsynaptic receptor activation is the most diversified step of synaptic transmission. Table 1 shows selected neurotransmitter receptors. 

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