G-protein-coupled receptors . See

G-proteins are trimeric, signal-transducing, guanine nucleotide-binding proteins. They constitute the first step in transducing the agonist-induced activation of a G-protein-coupled receptor (see Chapter 2) to a cellular response. 

There are various G-proteins that differ mainly with regard to their a-unit Association with the receptor activates the G-protein, leading in turn to activation of another protein (enzyme, ion channel). A large number of mediator substances act via G-protein-coupled receptors (see p. 66 for more details). 

S-pBlmrtovI (S-Acy11 tieterotrimeric G-proteins a-sjbunit), G-protein-coupled receptors, see chapter 5 Has proteins, see chapter 8 internal, no distinct consensus sequence... 

Vasopressin activates two subtypes of G protein-coupled receptors (see Chapter 17). Vi receptors are found on vascular smooth muscle cells and mediate vasoconstriction. V2 receptors are found on renal tubule cells and reduce diuresis through increased water permeability and water resorption in the collecting tubules. Extrarenal V2-like receptors regulate the release of coagulation factor VIII and von Willebrand factor. 

Some effects of prostaglandins are mediated through cell surface G-protein coupled receptors (see Chapter ll).306 Some other prostanoids bind to and activate nuclear peroxisome proliferator-activated receptors.306 PGJ2 may inhibit fatty acid synthesis and fat deposition in adipose tissue through these receptors. Some of the prostanoid derivatives enter membranes and may become incorporated into phospholipids and exert their effects there. 

Eerrg Y, Broder CC, Kennedy PE, Berger EA (1996) HIV-1 entry cofactor Functional cDNA clorrirrg of a seven-transmembrarre, G protein-coupled receptor [see commerrts]. Science 272 872-877. 

Endogenous opioid peptides (endorphins, dynor-phins, enkephalins), have been termed the brain s own morphine. Their discovery in 1972 explained why the brain has opioid receptors when there were no opioids in the body. These peptides attach to specific opioid receptors, mainly p (mu), 5 (delta) or K (kappa) located at several spinal and multiple supraspinal sites in the CNS. Opioid receptors are part of the family of G-protein-coupled receptors (see p. 91) and act to open potassium channels and prevent the opening of voltage-gated calcium channels which reduces neuronal excitability and inhibits the release of pain neurotransmitters, including substance P. 

Gfdy dimers directly activate the PI3-kinase / and y subtypes. In this way, a variety of extracellular signals can be transmitted via G protein-coupled receptors (see Section 5.5.5) and G proteins to PI3-kinase and its effectors. 

G-protein coupled receptors (.see below) fomi ti family of receptors with seven membrane-spanning helices. Tliey are linked (usually) to physiological rcspoiise.s by second messengers. 

The biological effects of chemokines are mediated by the interaction of these soluble proteins with their specific receptors, which belong to the superfamily of seven-transmembrane G-protein-coupled receptors (see Chap. 2). Similar to the chemokines themselves, the number of novel chemokine receptors identified has expanded rapidly. To date, 11 CC, 6 CXC, 1 CX3C, and 1 C-chemokine receptors have been characterized (2). The extracellular domain consists of an NHj-terminus and three extracellular loops, which act in concert to bind to the chemokine ligand. The intracellular region is composed of three loops and the COOH-terminus, which transduce the chemokine signal and regulate expression of the receptor (2). 

Nicotinic and muscarinic effects are mediated by nicotinic and muscarinic receptors, respectively. These receptors are the products of two distinct gene super-families, and their only common prc eity is that bey are activated by A. The slower muscarinic receptor response operates via G-protein-coupled receptors (see G-proteins). Depending on the receptor subtype, the suteequent effector mechanism involves inhibition of adenylate cyclase, formation of inositol 1,4,5-(ruphosphate from phosphoinositides by a specific phospholipase C, or modulation (opening) of certain K channels [D. Brown Nature 319 (1986) 358-359]. 

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