G-protein-coupled receptors functions

Overton, M. C. and Blumer, K. J. (2000). G-protein-coupled receptors function as oligomers in vivo. Curr. Biol. 10, 341-4. 

Rana, B. K., Shiina, T., and Insel, P. A. (2001) Genetic variations and polymorphisms of G protein-coupled receptors Functional and therapeutic implications. Annu. Rev. Pharmacol. Toxicol. 41, 593-624. 

Schoneberg, T., Schulz, A., and Gudermann, T. (2002) The structural basis of G-protein-coupled receptor function and dysfunction in human diseases. Rev. Physiol. Biochem. Pharmacol. 144, 143-227. 

Rohrer DK, Kobilka BK (1998) G protein-coupled receptors functional and mechanistic insights through altered gene expression. Physiol Rev 78 35-52 Rosin DL, Talley EM, Lee A, Stornetta RL, Gaylinn BD, Guyenet PG, Lynch KR (1996) Distribution of aj -adrenergic receptor like immunoreactivity in the rat central nervous system. J Comp Neurol 372 135-165 Ruffolo RR, Nichols AJ, Stadel ]M, Hieble JP (1993) Pharmacologic and therapeutic applications of a2-adrenoceptor subtypes. Aim Rev Pharmacol Toxicol 32 243-279... 

Qanbar, R., and Bouvier, M. (2003). Role of palmitoylation/depalmitoylation reactions in G-protein-coupled receptor function. Pharmacol. Ther. 97, 1-33. 

G protein-coupled receptors function as adapters between the virtually boundless multitude and variety of extracellular hormone and neurotransmitter signals and the lower (yet still considerable) number of intracellular G-proteins. Therefore, it is very common to have receptors for multiple transmitters or hormones converge onto the same type of G protein and thus trigger the same response. E g., glucagon and epinephrine both activate adenylate cyclase in the liver, through separate receptors but the very same G protein. 

Carrillo JJ, Pediani J, Milligan G. Dimers of class A G protein-coupled receptors function via agonist-mediated trans-activation of associated G proteins. J Biol Chem 2003 278 42,578-42,587. 

Like all regulatory GTPases, the heterotrimeric G proteins run through a cyclical transition between an inactive, GDP-bound form and an active, GTP-bound form. Thereby, the activated G protein-coupled receptor functions as a nucleotide exchange factor, GEF. Figure 5.18 sketches the different functional states and the role of the individual subunits. 

Sarid R, Sato T, Bohenzky RA, Russo JJ, Chang Y (1997) Kaposi s sarcoma-associated herpesvirus encodes a functional Bcl-2 homologue. Nature Medicine 3 293 298 Schoneberg T, Schultz G, Gudermann T (1999) Structural basis of G protein-coupled receptor function. Mol Cell Endocrinol 151 181-193... 

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. 

The family of apelin peptides is derived from a single gene, activate a single G-protein-coupled receptor and are substrates for the angiotensin converting enzyme-2 (ACE2). Apelins regulate cardiovascular function and fluid homeostasis. The apelin receptor also functions as a co-receptor for infection of CD4-positive cells by human immunodeficiency vims ( HIV). 

GABAb receptors mediate the slow and prolonged physiological effects of the inhibitory neurotransmitter GABA. Functional GABAb receptors are comprised of two subunits, GABAbR1 and GABAbR2. Both subunits are G-protein-coupled receptors, which couple to the Gi/o family and are densely expressed at spinal nociceptive synapses. 

Ly sophosphatidic acid (LPA) is the prototype of a group of bioactive lysophospholipids that act on specific G-protein-coupled receptors to mediate a wide variety of cellular functions. 

Muscarinic acetylcholine receptors (mAChRs) form a class of cell surface receptors that are activated upon binding of the neurotransmitter, acetylcholine. Structurally and functionally, mAChRs are prototypical members of the superfamily of G protein-coupled receptors. Following acetylcholine binding, the activated mAChRs interact with distinct classes of heterotrimeric G proteins resulting in the activation or inhibition of distinct downstream signaling cascades. 

Neuromedin U is a neuropeptide which is widely distributed in the gut and central nervous system. Peripheral activities of neuromedin U include stimulation of smooth muscle, increase in blood pressure, alteration of ion transport in the gut, control of local blood flow and regulation of adrenocortical function. The actions of neuromedin U are mediated by G-protein coupled receptors (NMU1, NMU2) which are coupled tO Gq/11. 

Sensory receptors that structurally and functionally belong to the G protein coupled receptor superfamily. Olfactory receptors are a large GPCR family with >300 members in human that are expressed in neurons of the nasal olfactory epithelium where they sense mostly volatile olfactory molecule. The overall number of olfactory receptors differs widely between species and an expansion of different recqrtors is in particular obvious in species that depend on their olfactory sense for survival. 

Pituitary Adenylyl Cyclase-activating Polypeptide (PACAP) is a 38-amino acid peptide (PACAP-38), which is widely expressed in the central nervous system. PACAP is most abundant in the hypothalamus. It is also found in the gastrointestinal tract, the adrenal gland and in testis. Its central nervous system functions are ill-defined. In the periphery, PACAP has been shown to stimulate catecholamine secretion from the adrenal medulla and to regulate secretion from the pancreas. Three G-protein coupled receptors have been shown to respond to PACAP, PAQ (PACAP type I) specifically binds PACAP, VPACi and VPAC2 also bind vasoactive intestinal peptide (VDP). Activation of PACAP receptors results in a Gs-mediated activation of adenylyl cyclase. 

Yang LV, Radu CG, Roy M et al (2007) Vascular abnormalities in mice deficient for the G Protein-coupled receptor GPR4 that functions as a pH sensor. Mol Cell Biol 27 1334-1347... 

Somatostatin is a regulatory cyclic peptide, which has originally been described as a hypothalamic growth hormone release-inhibiting factor. It is produced throughout the central nervous system (CNS) as well as in secretoty cells of the periphery and mediates its regulatory functions on cellular processes such as neurotransmission, smooth muscle contraction, secretion and cell proliferation via a family of seven transmembrane domain G-protein-coupled receptors termed sstx 5. 

Somatostatin acts on various organs, tissues and cells as neurotransmitter, paracrine/autocrine and endocrine regulator on cell secretion, smooth muscle contractility, nutrient absorption, cell growth and neurotransmission [1]. Some of its mainly inhibitory effects are listed in Table 1. Somatostatin mediates its function via a family of heptahelical G-protein-coupled receptors termed... 

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