G-protein-coupled transmembrane

W. H. Discovery of nanomolar ligands for 7-transmembrane G-protein-coupled receptors from a diverse N-(substi-tuted)glycine peptoid library. J. Med. Chem. 1994, 37, 2678-2685. 

The diverse actions of AM are mediated by the 7-transmembrane G protein-coupled calcitonin receptor-like receptor (CRLR) which coassembles with subtypes 2 and 3 of a family of receptor-activity-modifying proteins (RAMPs), thus forming a receptor-coreceptor system. Binding of AM to CRLR activates Gs and triggers cAMP formation in vascular smooth muscle cells, and increases nitric oxide production in endothelial cells. Other signaling pathways are also involved. 

Prostanoid receptors and their signaling pathways. fMLP, formylated MetLeuPhe, a small peptide receptor PLC-3, phospholipase C-3. All of the receptors shown are of the 7-transmembrane, G-protein coupled type. The terms "relaxant," "contractile," and "inhibitory" refer to the phylogenetic characterization of their primary effects. AII EP3 isoforms couple through G but some can also activate Gs or G12/13 pathways. RhoGEF, rho guanine nucleotide exchange factor. See text for additional details. 

Angiotensin peptides act at two main receptor types called AT] and ATj. In the rat and mouse, AT, and AT b receptors have been cloned and, though the product of different genes, have 94% homology, with small pharmacological and insignificant functional, differences. All these receptors are of the 7-transmembrane G-protein-coupled type. 

There are three distinct mammalian tachykinin receptors, termed NK, NK2 and NKj, all of which are of the 7-transmembrane G-protein-coupled superfamily, and which couple via the InsP DAG (Gq/n) pathway. These are produced by three or more separate genes. The orders of potency of the three principal endogenous peptides at the three receptors are as follows at NK, receptors, SP > NKA > NKB At NK2 receptors, NKA > NKB SP at NK3 receptors, NKB > NKA > SP. Thus each agonist can act at each receptor. 

Also, a number of other neuropeptides have also been shown to interfere with the expression of thirst subsequent to water deprivation and/or sodium appetite subsequent to sodium depletion. In some instances, ANG 11, presumably in the neural system subserving thirst, stimulates the release of a neuropeptide that inhibits the expression of sodium appetite. ANG II stimulates the release of oxytocin (Lang et al., 1981) and oxytocin appears to be one of the main inhibitory factors that limit the expression of sodium appetite (Stricker Verbalis, 1987 Verbalis, Blackburn, Hoffman, Stricker, 1995). Oxytocin is a 9-amino acid peptide synthesized in PVN or SON neurons that project either to the neurohypophysis or to sites within the central nervous system. Oxytocin receptors are part of the 7 transmembrane, G-protein-coupled receptor family (Barberis, Mouillac, Durroux, 1998) and are found in the BNST, nucleus ofthe solitary... 

Figure 13.7 7-Transmembrane G-protein coupled receptor protein...

The olfactory receptors belong to the 7-transmembrane-G-protein coupled family of receptors. A schematic structure is shown in Figure 10.6. They are coupled to G-proteins in the same way as is rhodopsin and generate the nerve signal through a similar second messenger system to that used by rhodopsin (see Chapter 8). They differ from rhodopsin in that they lack the additional tether back into the cell... 

G. M. Figliozzi, D. A. Goff, M. A. Siani, R. J. Simson, S. C. Banville, E. G. Brown, L. Wang, L. S. Richter, and W. H. Moos, J. Med. Chem., 37, 2678 (1994). Discovery of Nanomolar Ligands for 7-Transmembrane G-Protein-Coupled Receptors from a Diverse N-(Substi-tuted)Glycine Peptoid Library. 

The physiological and pharmacological effects of histamine are mediated through four different receptors Hi, Hj, Hj, and Ht, all members of the 7-transmembrane g protein-coupled receptor (GPCR) family with amino terminal glycosylation sites and phosphorylation sites for protein kinases A and C. The receptors are widely expressed on different tissues that are responsive to histamine. For the Hi receptor these tissues include smooth muscle cells of the airways and vasculature, the gastrointestinal tract, cardiovascular system, neutrophils, endothelial cells, T and B cells, hepatocy tes, nerve... 

---