Pub Date : 2000-03-01DOI: 10.1016/S0031-6865(99)00054-0
David J Triggle
Pharmacological receptors are typically defined by their selectivity of ligand recognition, including where appropriate stereoselectivity of interaction. It is increasingly clear that receptors may, in fact, be promiscuous species. This promiscuity arises at several levels of organization: two appear to be of particular importance. A given ligand–receptor complex may couple with different effectors and may generate quite different physiological responses: this is particularly common, although not uniquely so, for G protein-coupled receptors. Or a single receptor may recognize fundamentally different ligands often of significantly different characteristics: a number of viruses gain entry to cells through their interaction at receptors for neurotransmitters, peptides or hormones.
{"title":"Hijacked receptors","authors":"David J Triggle","doi":"10.1016/S0031-6865(99)00054-0","DOIUrl":"10.1016/S0031-6865(99)00054-0","url":null,"abstract":"<div><p>Pharmacological receptors are typically defined by their selectivity of ligand recognition, including where appropriate stereoselectivity of interaction. It is increasingly clear that receptors may, in fact, be promiscuous species. This promiscuity arises at several levels of organization: two appear to be of particular importance. A given ligand–receptor complex may couple with different effectors and may generate quite different physiological responses: this is particularly common, although not uniquely so, for G protein-coupled receptors. Or a single receptor may recognize fundamentally different ligands often of significantly different characteristics: a number of viruses gain entry to cells through their interaction at receptors for neurotransmitters, peptides or hormones.</p></div>","PeriodicalId":19830,"journal":{"name":"Pharmaceutica acta Helvetiae","volume":"74 2","pages":"Pages 287-290"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0031-6865(99)00054-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21659960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-03-01DOI: 10.1016/S0031-6865(99)00042-4
Rob Leurs, Maria Sol Rodriguez Pena, Remko A Bakker, Astrid E Alewijnse, Henk Timmerman
{"title":"Constitutive activity of G protein coupled receptors and drug action","authors":"Rob Leurs, Maria Sol Rodriguez Pena, Remko A Bakker, Astrid E Alewijnse, Henk Timmerman","doi":"10.1016/S0031-6865(99)00042-4","DOIUrl":"10.1016/S0031-6865(99)00042-4","url":null,"abstract":"","PeriodicalId":19830,"journal":{"name":"Pharmaceutica acta Helvetiae","volume":"74 2","pages":"Pages 327-331"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0031-6865(99)00042-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21660309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-03-01DOI: 10.1016/S0031-6865(99)00043-6
William F Simonds, Jian-Hua Zhang
The βγ complex of G-proteins regulates effectors independently of the Gα subunits, such that upon activation G proteins give may signal downstream along one or both pathways. The Gβ5 isoform exhibits much less homology with other Gβ isoforms (∼50%) and is preferentially expressed in brain. The Gβ5 isoform exhibits novel properties in its activation of effector pathways such as MAPK, phospholipase C-β, and adenylyl cyclase type II when compared to Gβ1. Recently specific native complexes between Gβ5 and the regulator of G protein signaling (RGS) protein-7 (RGS7) and between Gβ5L (a splice variant with a 42 amino acid N-terminal extension) and RGS9 have been isolated from different retinal fractions. Such findings are not accounted for by current models as only the Gα subunits and not Gβ had been previously implicated in RGS protein function. These recent novel observations further reinforce the view of Gβ5 as a unique and highly specialized G protein subunit.
{"title":"New dimensions in G protein signalling: Gβ5 and the RGS proteins","authors":"William F Simonds, Jian-Hua Zhang","doi":"10.1016/S0031-6865(99)00043-6","DOIUrl":"10.1016/S0031-6865(99)00043-6","url":null,"abstract":"<div><p><span>The βγ complex of G-proteins regulates effectors independently of the Gα subunits, such that upon activation G proteins give may signal downstream along one or both pathways. The Gβ</span><sub>5</sub> isoform exhibits much less homology with other Gβ isoforms (∼50%) and is preferentially expressed in brain. The Gβ<sub>5</sub><span> isoform exhibits novel properties in its activation of effector pathways such as MAPK, phospholipase C-β, and adenylyl cyclase type II when compared to Gβ</span><sub>1</sub>. Recently specific native complexes between Gβ5 and the regulator of G protein signaling (RGS) protein-7 (RGS7) and between Gβ<sub>5</sub><span>L (a splice variant with a 42 amino acid N-terminal extension) and RGS9 have been isolated from different retinal fractions. Such findings are not accounted for by current models as only the Gα subunits and not Gβ had been previously implicated in RGS protein function. These recent novel observations further reinforce the view of Gβ</span><sub>5</sub> as a unique and highly specialized G protein subunit.</p></div>","PeriodicalId":19830,"journal":{"name":"Pharmaceutica acta Helvetiae","volume":"74 2","pages":"Pages 333-336"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0031-6865(99)00043-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21660310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2000-03-01DOI: 10.1016/S0031-6865(99)00053-9
D.G Trist
Glutamic acid is the major excitatory neurotransmitter in the mammalian central nervous system (CNS). Specific receptors bind glutamate and some of these when activated open an integral ion channel and are thus known as ionotropic receptors. Within the ionotropic family of glutamate receptors, three major subtypes have been identified using classical specific agonist activation, selective competitive antagonists together with their structural heterogeneity. These receptors have thus been named N-methyl-d-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and kainate receptors. The NMDA receptor has sites in addition to its agonist-binding site and these seem to either positively or negatively modulate the agonist effect. The NMDA receptor also is unique in that another amino acid, glycine, acts as a co-agonist with glutamate. Changes in glutamate transmission have been associated with a number of CNS pathologies; these include, acute stroke, chronic neurodegeneration, chronic pain, depression, drug dependency, epilepsy, Parkinson's Disease and schizophrenia.
{"title":"Excitatory amino acid agonists and antagonists: pharmacology and therapeutic applications","authors":"D.G Trist","doi":"10.1016/S0031-6865(99)00053-9","DOIUrl":"10.1016/S0031-6865(99)00053-9","url":null,"abstract":"<div><p><span><span><span>Glutamic acid is the major excitatory </span>neurotransmitter in the mammalian central nervous system (CNS). Specific receptors bind glutamate and some of these when activated open an integral ion channel and are thus known as </span>ionotropic receptors<span><span>. Within the ionotropic family of glutamate receptors, three major subtypes have been identified using classical specific agonist activation, selective </span>competitive antagonists together with their structural heterogeneity. These receptors have thus been named </span></span><em>N</em>-methyl-<span>d</span><span><span><span>-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and kainate receptors. The NMDA receptor has sites in addition to its agonist-binding site and these seem to either positively or negatively modulate the agonist effect. The NMDA receptor also is unique in that another amino acid, glycine, acts as a co-agonist with glutamate. Changes in glutamate transmission have been associated with a number of CNS pathologies; these include, acute stroke, chronic neurodegeneration, chronic pain, depression, drug dependency, </span>epilepsy, </span>Parkinson's Disease and schizophrenia.</span></p></div>","PeriodicalId":19830,"journal":{"name":"Pharmaceutica acta Helvetiae","volume":"74 2","pages":"Pages 221-229"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0031-6865(99)00053-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21659338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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