Protein-coupled receptor

The G-proteins are heterotrimers made of three families of subunits, a, P, and y, which can interact specifically with discrete regions on G-protein-coupled receptors. This includes most receptors for neurotransmitters and polypeptide hormones (see Neuroregulators). G-protein-coupled receptors also embrace the odorant receptor family and the rhodopsin-linked visual cascade. 

A variety of cellular and viral proteins contain fatty acids covalently bound via ester linkages to the side chains of cysteine and sometimes to serine or threonine residues within a polypeptide chain (Figure 9.18). This type of fatty acyl chain linkage has a broader fatty acid specificity than A myristoylation. Myristate, palmitate, stearate, and oleate can all be esterified in this way, with the Cjg and Cjg chain lengths being most commonly found. Proteins anchored to membranes via fatty acyl thioesters include G-protein-coupled receptors, the surface glycoproteins of several viruses, and the transferrin receptor protein. 

Kenakin, T. P. (1997). Differences between natural and recombinant G-protein coupled receptor systems with varying receptor/G-protein stoichiometry. Trends Pharmacol. Sci. 18 456-464. 

The ternary complex model followed by the extended ternary complex model were devised to describe the action of drugs on G-protein-coupled receptors. 

One target type for which the molecular mechanism of efficacy has been partly elucidated is the G-protein-coupled receptor (GPCR). It is known that activation of GPCRs leads to an interaction of the receptor with separate membrane G-proteins to cause dissociation of the G-protein subunits and subsequent activation of effectors (see Chapter 2). For the purposes of binding, this process can lead to an aberration in the binding reaction as perceived in experimental binding studies. Specifically, the activation of the receptor with subsequent binding of that... 

Christopoulos, A. (2000). Quantification of allosteric interactions at G-protein coupled receptors using radioligand assays. In Current protocol in pharmacology, edited by Enna, S. J., pp. 1.22.21-1.22.40. Wiley and Sons, New York. 

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. 

Wildoer, M., Fong, J., Jones, R. M., Lunzer, M. M., Sharma, S. K., Kostensis, E., Portoghese, P. S., and Whistler, J. L. (2005). A heterodimer-selective agonist shows in vivo relevance of G-protein coupled receptor dimmers. Proc Natl. Acad. Sci. USA 102 9050-9055. 

Heptahelical receptors, another name for 7 TM receptors or G-protein-coupled receptors. It refers to the motif of the helices of the protein crossing the cell membrane seven times to form intracellular and extracellular domains. 

See G-protein = coupled receptors historical studies of, 2-4 operational model of, 45—47, 46f,... 

Adenosine is produced by many tissues, mainly as a byproduct of ATP breakdown. It is released from neurons, glia and other cells, possibly through the operation of the membrane transport system. Its rate of production varies with the functional state of the tissue and it may play a role as an autocrine or paracrine mediator (e.g. controlling blood flow). The uptake of adenosine is blocked by dipyridamole, which has vasodilatory effects. The effects of adenosine are mediated by a group of G protein-coupled receptors (the Gi/o-coupled Ai- and A3 receptors, and the Gs-coupled A2a-/A2B receptors). Ai receptors can mediate vasoconstriction, block of cardiac atrioventricular conduction and reduction of force of contraction, bronchoconstriction, and inhibition of neurotransmitter release. A2 receptors mediate vasodilatation and are involved in the stimulation of nociceptive afferent neurons. A3 receptors mediate the release of mediators from mast cells. Methylxanthines (e.g. caffeine) function as antagonists of Ai and A2 receptors. Adenosine itself is used to terminate supraventricular tachycardia by intravenous bolus injection. 

Extracellular adenosine acts through a class of G protein-coupled receptors (GPCRs), defined across mammalian species as Ab A2a, A2B, and A3ARs (adenosine receptors). Adenosine has a cytoprotective role in the body, both in the periphery and in the central nervous system. Following binding of adenosine, or another naturally occurring agonist, the receptor... 

Adrenaline (epinephrine) is a catecholamine, which is released as a neurotransmitter from neurons in the central nervous system and as a hormone from chromaffin cells of the adrenal gland. Adrenaline is required for increased metabolic and cardiovascular demand during stress. Its cellular actions are mediated via plasma membrane bound G-protein-coupled receptors. 

The biological actions of adrenaline and noradrenaline are mediated via nine different G-protein-coupled receptors, which are located in the plasma membrane of neuronal and nonneuronal target cells. These recqrtors are divided into two different groups, a-adrenergic receptors and P-adrenergic recqrtors (see P-adrenergic system). 

Cotecchia S et al (2004) Structural determinants involved in the activation and regulation of G protein-coupled receptors lessons from the ai -adrenergic receptor sub-types. Biol Cell 96 327-333... 

Recent studies indicate that - like many other receptors - G-protein-coupled receptors may form dimers, either homodimers or dimers with another type of receptor. The role of dimer formation in the cell surface expression of receptors and in their signalling and the resultant pharmacology are currently under intensive investigation [1]. 

Bulenger S, Marullo S, Bouvier M (2005) Emerging role of homo- and heterodimerization in G-protein-coupled receptor biosynthesis and maturation. Trends Pharmacol Sci 26 131-137... 

Opioids act on heptahelical G-protein-coupled receptors. Three types of opioid receptors (p, 8, k) have been cloned. Additional subtypes (e.g., pl3 p2, 81 82), possibly resulting from gene polymorphisms, splice variants or alternative processing have been proposed. Opioid receptors are localized and can be activated... 

G-protein-coupled Receptors Dopamine System Adenosine Receptors Chemokine Receptors... 

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