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The urea transporter (UT) family: bioinformatic analyses leading to structural, functional, and evolutionary predictions. 尿素转运体（UT）家族：结构、功能和进化预测的生物信息学分析。
Receptors & channels Pub Date : 2003-01-01 DOI: 10.3109/714041015
Ranjeet Minocha, Keith Studley, Milton H Saier
{"title":"The urea transporter (UT) family: bioinformatic analyses leading to structural, functional, and evolutionary predictions.","authors":"Ranjeet Minocha, Keith Studley, Milton H Saier","doi":"10.3109/714041015","DOIUrl":"10.3109/714041015","url":null,"abstract":"<p><p>We have identified all currently sequenced members of the urea transporter (UT) family (TC #1.A.28). Homologues occur exclusively in vertebrate animals and bacteria but not in other eukaryotic kingdoms or archaea. Sequence, structural, and phylogenetic analyses reveal conserved regions and residues and suggest that a primordial 5 transmembrane helical segment (TMS)-encoding genetic element duplicated to give a 10 TMS-encoding element early during evolutionary history, at about the time when eukaryotes diverged from prokaryotes. Two well-conserved, strongly amphipathic, putative alpha-helices that precede both 5 TMS repeat elements are predicted to be of structural, functional, or biogenic significance. A second duplication event (or a gene fusion event) occurred during development of the vertebrate lineage, giving rise to 20 TMS mammalian homologues. The results suggest that vertebrates acquired UT genetic information from bacteria only once and that all current orthologues and paralogues in the animal kingdom arose from this one primordial system.</p>","PeriodicalId":20928,"journal":{"name":"Receptors & channels","volume":"9 6","pages":"345-52"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/714041015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24143718","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}
引用次数: 32
Pharmacological analysis of the contractile role of M2 and M3 muscarinic receptors in smooth muscle. 平滑肌中M2和M3毒蕈碱受体收缩作用的药理学分析。
Receptors & channels Pub Date : 2003-01-01
Frederick J Ehlert
{"title":"Pharmacological analysis of the contractile role of M2 and M3 muscarinic receptors in smooth muscle.","authors":"Frederick J Ehlert","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Muscarinic receptors expressed on smooth muscle cells are primarily of the M(2) and M(3) subtypes. The M(3) subtype triggers contraction through an interaction with G(q) proteins to stimulate phosphoinositide hydrolysis and mobilize Ca(2+). In contrast, activation of M(2) receptors modulates contraction by preventing relaxation or by potentiating M(3) receptor-mediated contractions, which enhances heterologous desensitization. These effects can be explained by the coupling of M(2) receptors to G(i) proteins that mediate an inhibition of adenylyl cyclase and calcium-activated potassium channels. The pharmacological antagonism of a response mediated through an interaction between M(2) and M(3) receptors has been shown to resemble the profile of the directly acting receptor (M(3)), primarily, and not that of the conditional receptor (M(2)). Evidence for a contractile role of the M(2) receptor has been obtained by inactivating its signaling pathway with pertussis toxin or by measuring contractile effects of muscarinic agonists after M(3) receptors have been covalently inactivated. Under these conditions, M(2) receptors have been shown to mediate an inhibition of the relaxant effects of agents, like isoproterenol, on the contractile effects of nonmuscarinic spasmogens. Muscarinic M(2) and M(3) receptor knockout mice are useful tools for exploring interactions between these receptors in smooth muscle.</p>","PeriodicalId":20928,"journal":{"name":"Receptors & channels","volume":"9 4","pages":"261-77"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22510910","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}
引用次数: 0
Activity, regulation, and intracellular localization of RGS proteins. RGS蛋白的活性、调控和细胞内定位。
Receptors & channels Pub Date : 2003-01-01 DOI: 10.3109/10606820308244
P. Chidiac, A. A. Roy
{"title":"Activity, regulation, and intracellular localization of RGS proteins.","authors":"P. Chidiac, A. A. Roy","doi":"10.3109/10606820308244","DOIUrl":"https://doi.org/10.3109/10606820308244","url":null,"abstract":"RGS proteins attenuate the activities of heterotrimeric G proteins largely by promoting the hydrolysis of the activating nucleotide GTP. This review discusses the interactions of RGS proteins and G proteins and how those interactions are regulated by a variety of factors including auxiliary proteins and other cellular constituents, posttranslational modifications, and intracellular localization patterns. In addition, we discuss progress that has been made toward understanding the roles that RGS proteins play in vivo, and how they may serve to govern responses to G protein-coupled receptors upon acute and prolonged activation by agonists.","PeriodicalId":20928,"journal":{"name":"Receptors & channels","volume":"30 1","pages":"135-47"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87830803","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}
引用次数: 54
Protein complexes involved in heptahelical receptor-mediated signal transduction. 参与七螺旋受体介导的信号转导的蛋白质复合物。
Receptors & channels Pub Date : 2003-01-01
R Victor Rebois, Terence E Hébert
{"title":"Protein complexes involved in heptahelical receptor-mediated signal transduction.","authors":"R Victor Rebois,&nbsp;Terence E Hébert","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Signal transduction mediated by heterotrimeric G proteins that couple to heptahelical receptors requires the involvement of many different proteins. Although some of the early evidence suggested that signal transduction components were assembled into complexes, much of the data supported an alternative hypothesis positing that the process involved transient interactions driven by random collision events. However, recent data indicate that many of the components involved in signal transduction do indeed form complexes. Here we review the evidence for these complexes and how they contribute to the specificity and efficiency of signaling in cells that must manage numerous signal transduction pathways.</p>","PeriodicalId":20928,"journal":{"name":"Receptors & channels","volume":"9 3","pages":"169-94"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22409851","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}
引用次数: 0
Application of the Cytosensor microphysiometer to drug discovery. 细胞传感器微生理仪在药物发现中的应用。
Receptors & channels Pub Date : 2003-01-01
Kirsten Wille, Lisa A Paige, Alan J Higgins
{"title":"Application of the Cytosensor microphysiometer to drug discovery.","authors":"Kirsten Wille,&nbsp;Lisa A Paige,&nbsp;Alan J Higgins","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The Cytosensor microphysiometer uses silicon chip technology to correlate changes in extracellular acidification rates with quantitative changes in cellular metabolism in response to ligand binding to surface receptors. This functional measure of physiology makes the Cytosensor a valuable tool in drug discovery research by allowing application of the instrument to screening of prospective pharmacologically active agents, characterizations of dose responses and structure-activity relationships, and investigation of mechanisms of action.</p>","PeriodicalId":20928,"journal":{"name":"Receptors & channels","volume":"9 2","pages":"125-31"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22528641","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}
引用次数: 0
Introduction: an evolution of electrophysiology. 导言:电生理学的进化。
Receptors & channels Pub Date : 2003-01-01
Jennings Worley
{"title":"Introduction: an evolution of electrophysiology.","authors":"Jennings Worley","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":20928,"journal":{"name":"Receptors & channels","volume":"9 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22453414","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}
引用次数: 0
Accessory proteins for G protein-signaling systems: activators of G protein signaling and other nonreceptor proteins influencing the activation state of G proteins. G蛋白信号系统的辅助蛋白:G蛋白信号的激活因子和其他影响G蛋白激活状态的非受体蛋白。
Receptors & channels Pub Date : 2003-01-01 DOI: 10.1080/10606820308240
J. Blumer, S. Lanier
{"title":"Accessory proteins for G protein-signaling systems: activators of G protein signaling and other nonreceptor proteins influencing the activation state of G proteins.","authors":"J. Blumer, S. Lanier","doi":"10.1080/10606820308240","DOIUrl":"https://doi.org/10.1080/10606820308240","url":null,"abstract":"Heterotrimeric G proteins are key transducers for signal transfer from outside of the cell. In addition to their regulation by the superfamily of G protein-coupled receptors, many if not all of the subtypes of heterotrimeric G proteins are also regulated by additional accessory proteins that influence guanine nucleotide binding and/or hydrolysis or subunit interactions. Activators of G protein signaling (AGS1-3) refer to a functionally defined group of proteins that activate G protein-signaling systems in the absence of a classical G protein-coupled receptor. AGS and related proteins provide unexpected insights into the regulation of the G protein activation/deactivation cycle and the functional roles of G proteins. These proteins likely play important roles in the generation of signaling complexes, the positioning of signaling proteins within the cell, and in biological roles of G proteins unrelated to a cell surface receptor. As such, these proteins and the concepts advanced with their discovery provide unexpected avenues for therapeutics and understanding disease mechanisms.","PeriodicalId":20928,"journal":{"name":"Receptors & channels","volume":"2 1","pages":"195-204"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74432028","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}
引用次数: 39
Upscaling and automation of electrophysiology: toward high throughput screening in ion channel drug discovery. 电生理学的升级和自动化:迈向离子通道药物发现的高通量筛选。
Receptors & channels Pub Date : 2003-01-01 DOI: 10.3109/10606820308258
M. Asmild, Nicholas Oswald, K. Krzywkowski, S. Friis, R. B. Jacobsen, Dirk Reuter, R. Taboryski, Jonathan Kutchinsky, R. Vestergaard, R. L. Schrøder, C. Sørensen, M. Bech, Mads P. G. Korsgaard, N. Willumsen
{"title":"Upscaling and automation of electrophysiology: toward high throughput screening in ion channel drug discovery.","authors":"M. Asmild, Nicholas Oswald, K. Krzywkowski, S. Friis, R. B. Jacobsen, Dirk Reuter, R. Taboryski, Jonathan Kutchinsky, R. Vestergaard, R. L. Schrøder, C. Sørensen, M. Bech, Mads P. G. Korsgaard, N. Willumsen","doi":"10.3109/10606820308258","DOIUrl":"https://doi.org/10.3109/10606820308258","url":null,"abstract":"Effective screening of large compound libraries in ion channel drug discovery requires the development of new electrophysiological techniques with substantially increased throughputs compared to the conventional patch clamp technique. Sophion Bioscience is aiming to meet this challenge by developing two lines of automated patch clamp products, a traditional pipette-based system called Apatchi-1, and a silicon chip-based system QPatch. The degree of automation spans from semi-automation (Apatchi-1) where a trained technician interacts with the system in a limited way, to a complete automation (QPatch 96) where the system works continuously and unattended until screening of a full compound library is completed. The performance of the systems range from medium to high throughputs.","PeriodicalId":20928,"journal":{"name":"Receptors & channels","volume":"40 1","pages":"49-58"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91272249","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}
引用次数: 28
Biophysical properties of Kv3.1 channels in SH-SY5Y human neuroblastoma cells. SH-SY5Y人神经母细胞瘤细胞中Kv3.1通道的生物物理特性
Receptors & channels Pub Date : 2003-01-01 DOI: 10.3109/714041019
P Friederich, J P Dilger, D Isbrandt, K Sauter, O Pongs, B W Urban
{"title":"Biophysical properties of Kv3.1 channels in SH-SY5Y human neuroblastoma cells.","authors":"P Friederich,&nbsp;J P Dilger,&nbsp;D Isbrandt,&nbsp;K Sauter,&nbsp;O Pongs,&nbsp;B W Urban","doi":"10.3109/714041019","DOIUrl":"https://doi.org/10.3109/714041019","url":null,"abstract":"<p><p>Biophysical properties of delayed rectifier K channels in the human neuroblastoma SH-SY5Y were established using patch clamp recordings. The whole cell K+ conductance activated at membrane potentials positive to -20 mV. The midpoint of current activation was 9.6 +/- 5.1 mV, the equivalent charge was 3.7 +/-.6. Whole-cell currents inactivated slightly with time constants of 700 ms and 5 s. The K+ currents were sensitive to micromolar concentrations of TEA and 4-aminopyridine. RT-PCR experiments amplified a cDNA fragment specific for human Kv3.1 channels. Activation gating parameters in outside-out patches were shifted by approximately 14 mV in the hyperpolarizing direction.</p>","PeriodicalId":20928,"journal":{"name":"Receptors & channels","volume":"9 6","pages":"387-96"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/714041019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24144766","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}
引用次数: 12
Properties of Arg389-beta1-adrenoceptor-Gsalpha fusion proteins: comparison with Gly389-beta1-adrenoceptor-Gsalpha fusion proteins. arg389 - β -肾上腺素受体- gsalpha融合蛋白的特性:与gly389 - β -肾上腺素受体- gsalpha融合蛋白的比较
Receptors & channels Pub Date : 2003-01-01 DOI: 10.3109/713745179
Katharina Wenzel-Seifert, Roland Seifert
{"title":"Properties of Arg389-beta1-adrenoceptor-Gsalpha fusion proteins: comparison with Gly389-beta1-adrenoceptor-Gsalpha fusion proteins.","authors":"Katharina Wenzel-Seifert,&nbsp;Roland Seifert","doi":"10.3109/713745179","DOIUrl":"https://doi.org/10.3109/713745179","url":null,"abstract":"<p><p>The human beta1-adrenoceptor (beta1AR) exists in several isoforms and activates adenylyl cyclase (AC) via Gs-proteins. The Arg389-isoform of the beta1AR (beta1AR-R389) expressed in CHW cells is much more efficient than the Gly389 isoform of the beta1AR (beta1AR-G389) at stabilizing the ternary complex and activating AC (Mason et al. 1999). The beta1AR-G389 fused to the Gsalpha splice variants GsalphaL or GsalphaS is efficient at stabilizing the ternary complex and activating AC (Wenzel-Seifert et al. 2002). Here, we show that beta1AR-R389-Gsalpha fusion proteins and beta1AR-G389-Gsalpha fusion proteins are similarly efficient at stabilizing the ternary complex and activating AC. In terms of agonist efficacies and agonist potencies in the [35S]guanosine 5'-O-(3-thiotriphosphate) binding assay, beta1AR-R389-Gsalpha fusion proteins and beta1AR-G389-Gsalpha fusion proteins are similar, too. Our present data fit to an increasing number of clinical studies that failed to detect physiology- or pathology-related functional differences between beta1AR-R389 and beta1AR-G389.</p>","PeriodicalId":20928,"journal":{"name":"Receptors & channels","volume":"9 5","pages":"315-23"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/713745179","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24013768","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}
引用次数: 10
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