IUPHAR/BPS Guide to Pharmacology CITE http://journals.ed.ac.uk/gtopdb-cite <p>This journal is designed to house citation summaries for contributions to the <a href="http://www.guidetopharmacology.org" target="_blank" rel="noopener">IUPHAR/BPS Guide to Pharmacology (GtoPdb) database</a>. The journal is not open to general submissions, only curators of the GtoPdb can submit to the journal. The citation summaries exist as an adjunct to the database to facilitate the recognition of citations to and from the database by citation analysers.</p> <p>&nbsp;</p> en-US enquiries@guidetopharmacology.org (Dr. Simon Harding) openaccess@ed.ac.uk (Scholarly Communications Team, Edinburgh University Library) Wed, 13 Nov 2019 00:00:00 +0000 OJS 3.1.1.2 http://blogs.law.harvard.edu/tech/rss 60 Chemokine receptors (version 2019.5) in the IUPHAR/BPS Guide to Pharmacology Database http://journals.ed.ac.uk/gtopdb-cite/article/view/4090 <p>Chemokine receptors (<b>nomenclature as agreed by the <u>NC-IUPHAR</u> Subcommittee on Chemokine Receptors [<a href="http://www.ncbi.nlm.nih.gov/pubmed/10699158?dopt=AbstractPlus">426</a>, <a href="http://www.ncbi.nlm.nih.gov/pubmed/12037138?dopt=AbstractPlus">425</a>, <a href="http://www.ncbi.nlm.nih.gov/pubmed/24218476?dopt=AbstractPlus">32</a>]</b>) comprise a large subfamily of 7TM proteins that bind one or more chemokines, a large family of small cytokines typically possessing chemotactic activity for leukocytes. Additional hematopoietic and non-hematopoietic roles have been identified for many chemokines in the areas of embryonic development, immune cell proliferation, activation and death, viral infection, and as antibiotics, among others. Chemokine receptors can be divided by function into two main groups: G protein-coupled chemokine receptors, which mediate leukocyte trafficking, and "Atypical chemokine receptors", which may signal through non-G protein-coupled mechanisms and act as chemokine scavengers to downregulate inflammation or shape chemokine gradients [<a href="http://www.ncbi.nlm.nih.gov/pubmed/24218476?dopt=AbstractPlus">32</a>].<br><br>Chemokines in turn can be divided by structure into four subclasses by the number and arrangement of conserved cysteines. CC (also known as &#946;-chemokines; <i>n</i>= 28), CXC (also known as <em>&#945;</em>-chemokines; <i>n</i>= 17) and CX3C (<i>n</i>= 1) chemokines all have four conserved cysteines, with zero, one and three amino acids separating the first two cysteines respectively. C chemokines (<i>n</i>= 2) have only the second and fourth cysteines found in other chemokines. Chemokines can also be classified by function into homeostatic and inflammatory subgroups. Most chemokine receptors are able to bind multiple high-affinity chemokine ligands, but the ligands for a given receptor are almost always restricted to the same structural subclass. Most chemokines bind to more than one receptor subtype. Receptors for inflammatory chemokines are typically highly promiscuous with regard to ligand specificity, and may lack a selective endogenous ligand. G protein-coupled chemokine receptors are named acccording to the class of chemokines bound, whereas ACKR is the root acronym for atypical chemokine receptors [<a href="http://www.ncbi.nlm.nih.gov/pubmed/25958743?dopt=AbstractPlus">33</a>]. There can be substantial cross-species differences in the sequences of both chemokines and chemokine receptors, and in the pharmacology and biology of chemokine receptors. Endogenous and microbial non-chemokine ligands have also been identified for chemokine receptors. Many chemokine receptors function as HIV co-receptors, but CCR5 is the only one demonstrated to play an essential role in HIV/AIDS pathogenesis. The tables include both standard chemokine receptor names [<a href="http://www.ncbi.nlm.nih.gov/pubmed/10714678?dopt=AbstractPlus">675</a>] and aliases.</p> Francoise Bachelerie, Adit Ben-Baruch, Israel F. Charo, Christophe Combadiere, Reinhold Förster, Joshua M. Farber, Gerard J. Graham, Rebecca Hills, Richard Horuk, Massimo Locati, Andrew D. Luster, Alberto Mantovani, Kouji Matsushima, Amy E. Monaghan, Georgios L. Moschovakis, Philip M. Murphy, Robert J. B. Nibbs, Hisayuki Nomiyama, Joost J. Oppenheim, Christine A. Power, Amanda E. I. Proudfoot , Mette M. Rosenkilde, Antal Rot, Silvano Sozzani, Marcus Thelen, Mohib Uddin, Osamu Yoshie, Albert Zlotnik ##submission.copyrightStatement## http://creativecommons.org/licenses/by-sa/4.0 http://journals.ed.ac.uk/gtopdb-cite/article/view/4090 Wed, 13 Nov 2019 00:00:00 +0000 Class A Orphans (version 2019.5) in the IUPHAR/BPS Guide to Pharmacology Database http://journals.ed.ac.uk/gtopdb-cite/article/view/4091 <div><p>Table 1 lists a number of putative GPCRs identified by <b> <u>NC-IUPHAR</u> [<a href="http://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlus">194</a>]</b>, for which preliminary evidence for an endogenous ligand has been published, or for which there exists a potential link to a disease, or disorder. These GPCRs have recently been reviewed in detail [<a href="http://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlus">150</a>]. The GPCRs in Table 1 are all Class A, rhodopsin-like GPCRs. Class A orphan GPCRs not listed in Table 1 are putative GPCRs with as-yet unidentified endogenous ligands.<br><br><b>Table 1</b>: Class A orphan GPCRs with putative endogenous ligands<br> </p><table class="tableizer-table"> <tr><td><a href="https://www.guidetopharmacology.org/GRAC/#83"><i>GPR3</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#84"><i>GPR4</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#85"><i>GPR6</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#86"><i>GPR12</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#87"><i>GPR15</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#88"><i>GPR17</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#91"><i>GPR20</i></a></td></tr> <tr><td><a href="https://www.guidetopharmacology.org/GRAC/#93"><i>GPR22</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#96"><i>GPR26</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#98"><i>GPR31</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#101"><i>GPR34</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#102"><i>GPR35</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#103"><i>GPR37</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#105"><i>GPR39</i></a></td></tr> <tr><td><a href="https://www.guidetopharmacology.org/GRAC/#107"><i>GPR50</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#112"><i>GPR63</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#113"><i>GRP65</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#114"><i>GPR68</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#115"><i>GPR75</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#120"><i>GPR84</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#122"><i>GPR87</i></a></td></tr> <tr><td><a href="https://www.guidetopharmacology.org/GRAC/#123"><i>GPR88</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#128"><i>GPR132</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#135"><i>GPR149</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#141"><i>GPR161</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#81"><i>GPR183</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#147"><i>LGR4</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#148"><i>LGR5</i></a></td></tr> <tr><td><a href="https://www.guidetopharmacology.org/GRAC/#149"><i>LGR6</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#150"><i>MAS1</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#152"><i>MRGPRD</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#156"><i>MRGPRX1</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#157"><i>MRGPRX2</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#165"><i>P2RY10</i></a></td><td><a href="https://www.guidetopharmacology.org/GRAC/#167"><i>TAAR2</i></a></td></tr> </table> <br>In addition the orphan receptors <a href="https://www.guidetopharmacology.org/GRAC/#89"><i>GPR18</i></a>, <a href="https://www.guidetopharmacology.org/GRAC/#109"><i>GPR55</i></a> and <a href="https://www.guidetopharmacology.org/GRAC/#126"><i>GPR119</i></a> which are reported to respond to endogenous agents analogous to the endogenous cannabinoid ligands have been grouped together (<a href="https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=114">GPR18, GPR55 and GPR119</a>).</div> Stephen P.H. Alexander, Jim Battey, Helen E. Benson, Richard V. Benya, Tom I. Bonner, Anthony P. Davenport, Satoru Eguchi, Anthony Harmar, Nick Holliday, Robert T. Jensen, Sadashiva Karnik, Evi Kostenis, Wen Chiy Liew, Amy E. Monaghan, Chido Mpamhanga, Richard Neubig, Adam J. Pawson, Jean-Philippe Pin, Joanna L. Sharman, Michael Spedding, Eliot Spindel, Leigh Stoddart, Laura Storjohann, Walter G. Thomas, Kalyan Tirupula, Patrick Vanderheyden ##submission.copyrightStatement## http://creativecommons.org/licenses/by-sa/4.0 http://journals.ed.ac.uk/gtopdb-cite/article/view/4091 Wed, 13 Nov 2019 00:00:00 +0000 Prostanoid receptors (version 2019.5) in the IUPHAR/BPS Guide to Pharmacology Database http://journals.ed.ac.uk/gtopdb-cite/article/view/4092 <p>Prostanoid receptors (<b>nomenclature as agreed by the <u>NC-IUPHAR</u> Subcommittee on Prostanoid Receptors [<a href="http://www.ncbi.nlm.nih.gov/pubmed/21752876?dopt=AbstractPlus">659</a>]</b>) are activated by the endogenous ligands prostaglandins <a href="http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1881">PGD<sub>2</sub></a>, <a href="http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1882">PGE<sub>1</sub></a>, <a href="http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1883">PGE<sub>2</sub></a> , <a href="http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1884">PGF<sub>2&#945;</sub></a>, <a href="http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4483">PGH<sub>2</sub></a>, prostacyclin [<a href="http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1915">PGI<sub>2</sub></a>] and <a href="http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4482">thromboxane A<sub>2</sub></a>. Measurement of the potency of <a href="http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1915">PGI<sub>2</sub></a> and <a href="http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4482">thromboxane A<sub>2</sub></a> is hampered by their instability in physiological salt solution; they are often replaced by <a href="http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1917">cicaprost</a> and <a href="http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1888">U46619</a>, respectively, in receptor characterization studies.</p> Richard M. Breyer, Lucie Clapp, Robert A. Coleman, Mark Giembycz, Akos Heinemann, Rebecca Hills, Robert L. Jones, Shuh Narumiya, Xavier Norel, Roy Pettipher, Yukihiko Sugimoto, Mohib Uddin, David F. Woodward, Chengcan Yao ##submission.copyrightStatement## http://creativecommons.org/licenses/by-sa/4.0 http://journals.ed.ac.uk/gtopdb-cite/article/view/4092 Wed, 13 Nov 2019 00:00:00 +0000 Eicosanoid turnover (version 2019.5) in the IUPHAR/BPS Guide to Pharmacology Database http://journals.ed.ac.uk/gtopdb-cite/article/view/4093 <p>Eicosanoids are 20-carbon fatty acids, where the usual focus is the polyunsaturated analogue <a href="http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2391">arachidonic acid</a> and its metabolites. Arachidonic acid is thought primarily to derive from <a href="https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=244#Phospholipase%20A2">phospholipase A2</a> action on membrane phosphatidylcholine, and may be re-cycled to form phospholipid through conjugation with <a href="http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3044">coenzyme A</a> and subsequently glycerol derivatives. Oxidative metabolism of arachidonic acid is conducted through three major enzymatic routes: cyclooxygenases; lipoxygenases and cytochrome P450-like epoxygenases, particularly <a href="https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=242#show_object_1332">CYP2J2</a>. Isoprostanes are structural analogues of the prostanoids (hence the nomenclature D-, E-, F-isoprostanes and isothromboxanes), which are produced in the presence of elevated free radicals in a non-enzymatic manner, leading to suggestions for their use as biomarkers of oxidative stress. Molecular targets for their action have yet to be defined.</p> Angelo A. Izzo, Jane A. Mitchell ##submission.copyrightStatement## http://creativecommons.org/licenses/by-sa/4.0 http://journals.ed.ac.uk/gtopdb-cite/article/view/4093 Wed, 13 Nov 2019 00:00:00 +0000 Hydrolases (version 2019.5) in the IUPHAR/BPS Guide to Pharmacology Database http://journals.ed.ac.uk/gtopdb-cite/article/view/4094 <p>Listed in this section are hydrolases not accumulated in other parts of the Concise Guide, such as monoacylglycerol lipase and acetylcholinesterase. Pancreatic lipase is the predominant mechanism of fat digestion in the alimentary system; its inhibition is associated with decreased fat absorption. CES1 is present at lower levels in the gut than CES2 <a href="http://www.uniprot.org/uniprot/P23141" target="_blank">(P23141</a>), but predominates in the liver, where it is responsible for the hydrolysis of many aliphatic, aromatic and steroid esters. Hormone-sensitive lipase is also a relatively non-selective esterase associated with steroid ester hydrolysis and triglyceride metabolism, particularly in adipose tissue. Endothelial lipase is secreted from endothelial cells and regulates circulating cholesterol in high density lipoproteins.</p> Stephen P.H. Alexander, Patrick Doherty, David Fairlie, Christopher J. Fowler, Christopher M. Overall, Neil Rawlings, Christopher Southan, Anthony J. Turner ##submission.copyrightStatement## http://creativecommons.org/licenses/by-sa/4.0 http://journals.ed.ac.uk/gtopdb-cite/article/view/4094 Wed, 13 Nov 2019 00:00:00 +0000 E3 ubiquitin ligase components (version 2019.5) in the IUPHAR/BPS Guide to Pharmacology Database http://journals.ed.ac.uk/gtopdb-cite/article/view/4095 <p>Ubiquitination (a.k.a. ubiquitylation) is a protein post-translational modification that typically requires the sequential action of three enzymes: E1 (ubiquitin-activating enzymes), E2 (ubiquitin-conjugating enzymes), and E3 (ubiquitin ligases) [<a href="http://www.ncbi.nlm.nih.gov/pubmed/27015313?dopt=AbstractPlus">16</a>]. Ubiquitination of proteins can target them for proteasomal degradation, or modulate cellular processes including cell cycle progression, transcriptional regulation, DNA repair and signal transduction.<br> E3 ubiquitin ligases, of which there are &gt;600 in humans, are a family of highly heterogeneous proteins and protein complexes that recruit ubiquitin-loaded E2 enzymes to mediate transfer of the ubiquitin molecule from the E2 to protein substrates. Target substrate specificity is determined by a substrate recognition subunit within the E3 complex.</p> Elena Faccenda, Robert Layfield ##submission.copyrightStatement## http://creativecommons.org/licenses/by-sa/4.0 http://journals.ed.ac.uk/gtopdb-cite/article/view/4095 Wed, 13 Nov 2019 00:00:00 +0000