Receptors & channels最新文献_第10页

High Throughput Electrophysiology Using a Fully Automated, Multiplexed Recording System 高通量电生理使用全自动，多路记录系统

Receptors & channels Pub Date : 2003-01-01 DOI: 10.1080/10606820308252

J. D. Trumbull, E. Maslana, D. Mckenna, Thomas A. Nemcek, W. Niforatos, Jeffrey Y. Pan, A. Parihar, C. Shieh, Julie A. Wilkins, C. Briggs, D. Bertrand

{"title":"High Throughput Electrophysiology Using a Fully Automated, Multiplexed Recording System","authors":"J. D. Trumbull, E. Maslana, D. Mckenna, Thomas A. Nemcek, W. Niforatos, Jeffrey Y. Pan, A. Parihar, C. Shieh, Julie A. Wilkins, C. Briggs, D. Bertrand","doi":"10.1080/10606820308252","DOIUrl":"https://doi.org/10.1080/10606820308252","url":null,"abstract":"The drug discovery process centers around finding and optimizing novel compounds active at therapeutic targets. This process involves direct and indirect measures of how compounds affect the behavior of the target in question. The sheer number of compounds that must be tested poses problems for classes of ion channel targets for which direct functional measurements (e.g., traditional patch-clamping) are too cumbersome and indirect measurements (e.g., Ca(2+)-sensitive dyes) lack sufficient sensitivity or require unacceptable compromises. We present an optimized process for obtaining large numbers of direct electrophysiological measurements (two-electrode voltage-clamp) from Xenopus oocytes using a combination of automated oocyte handling, efficient and flexible liquid delivery, parallel operation, and powerful integrated data analysis. These improvements have had a marked impact, increasing the contribution electrophysiology makes in optimizing lead compound series and the discovery of new ones. The design of the system is detailed along with examples of data generated in support of lead optimization and discovery.","PeriodicalId":20928,"journal":{"name":"Receptors & channels","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82227883","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: 21

The roboocyte: automated cDNA/mRNA injection and subsequent TEVC recording on Xenopus oocytes in 96-well microtiter plates. 爪蟾卵母细胞:在96孔微滴板上自动注射cDNA/mRNA并随后进行TEVC记录。

Receptors & channels Pub Date : 2003-01-01 DOI: 10.3109/10606820308253

K. Schnizler, Mike Küster, C. Methfessel, M. Fejtl

{"title":"The roboocyte: automated cDNA/mRNA injection and subsequent TEVC recording on Xenopus oocytes in 96-well microtiter plates.","authors":"K. Schnizler, Mike Küster, C. Methfessel, M. Fejtl","doi":"10.3109/10606820308253","DOIUrl":"https://doi.org/10.3109/10606820308253","url":null,"abstract":"Membrane-bound neurotransmitter receptors and ion channels are among the most numerous and important drug targets, and electrophysiological methods are the gold standard for the study of their functional properties and their response to drugs. However, electrophysiological measurements are usually performed one at a time by highly skilled individuals, and secondary functional screening is often hampered by this lack of throughput. Accordingly, the use of automated procedures to increase the efficiency of electrophysiological techniques is of great interest. Among the many different electrophysiological techniques that have been described, two electrode voltage clamp recording (TEVC) from Xenopus oocytes seems particularly suitable for the implementation of automated measurement systems. Here, we describe a workstation that was expressly developed for this purpose. The Roboocyte is the first (and the only currently available) instrument that automatically performs both cDNA (or mRNA) injection and subsequent TEVC recording on Xenopus oocytes plated in a standard 96-well microtiter plate. This paper describes the scientific background of the oocyte expression system for drug screening and the development of the Roboocyte. Then, some technical details of the Roboocyte system are presented and, finally, results obtained with the Roboocyte are discussed with regard to increased throughput compared with manually performed experiments. Further information can be obtained at www.roboocyte.com.","PeriodicalId":20928,"journal":{"name":"Receptors & channels","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78704631","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: 60

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 DOI: 10.3109/10606820308246

K. Wille, L. A. Paige, A. J. Higgins

引用次数: 7

V2R structure and diabetes insipidus. V2R结构与尿崩症。

Receptors & channels Pub Date : 2002-01-01

Mariel Birnbaumer

{"title":"V2R structure and diabetes insipidus.","authors":"Mariel Birnbaumer","doi":"","DOIUrl":"","url":null,"abstract":"For most audiences, the term \"diabetes\" conjures thoughts of high levels of blood glucose and of the symptoms that characterize diabetes mellitus. In the last few years, a spirited campaign spear-headed by the families of affected individuals has made progress in educating nonprofessional and medical communities about diabetes insipidus (DI), the other disease characterized by polyuria (i.e., diabetes). Much work lies ahead to find better treatments for this affliction, but the progress in molecular biology over the last years made possible the identification of the genetic defects underlying the inherited forms of the disease. Numerous cases of adult-onset DI are triggered by toxic damage to the kidneys that impairs the concentrating capacity of the nephrons by a nonspecific mechanism. In these pages I shall deal mostly with the inherited forms of the disease. Diabetes insipidus is characterized by the inability of the kidneys of affected individuals to produce concentrated urine (Morello and Bichet 2001). The elimination of large volumes of diluted urine (polyuria) and excessive thirst (polydipsia) are the chief symptoms of the disease. Although this condition and the hints that it was a hereditary disease were described at the end of the 19th century, it took almost 100 years to gain molecular knowledge about its etiology. A brief review of the important role played by vasopressin in the maintenance of body fluids will help the reader understand the severity of this disease.","PeriodicalId":20928,"journal":{"name":"Receptors & channels","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22085600","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

The use of receptor G-protein fusion proteins for the study of ligand activity. 利用受体g蛋白融合蛋白研究配体活性。

Receptors & channels Pub Date : 2002-01-01 DOI: 10.3109/10606820214639

G. Milligan

引用次数: 18

Molecular pharmacology of the calcitonin receptor. 降钙素受体的分子药理学。

Receptors & channels Pub Date : 2002-01-01 DOI: 10.1080/10606820213681

B. Purdue, N. Tilakaratne, P. Sexton

引用次数: 97

Molecular pharmacology of class II G protein-coupled receptors. Introduction. ⅱ类G蛋白偶联受体的分子药理学。介绍。

Receptors & channels Pub Date : 2002-01-01

Patrick M Sexton

引用次数: 0

VPAC receptors for VIP and PACAP. VIP和PACAP的VPAC受体。

Receptors & channels Pub Date : 2002-01-01

M Laburthe, A Couvineau, J C Marie

引用次数: 0

Polymorphic G-protein-coupled receptors and associated diseases. 多态性g蛋白偶联受体与相关疾病。

Receptors & channels Pub Date : 2002-01-01

Dianne M Perez

引用次数: 0

Lack of sumatriptan-induced aortic contraction or relaxation: 5-HT1B receptor protein detected in endothelium and smooth muscle of vasa vasorum but not aorta. 素马匹坦缺乏诱导的主动脉收缩或舒张:血管内皮和血管平滑肌中检测到5-HT1B受体蛋白，但主动脉中未检测到。

Receptors & channels Pub Date : 2002-01-01

Marlene L Cohen, Elizabeth J Galbreath, Kathryn W Schenck, Danqing Li, Beth J Hoffman, Anindya Bhattacharya

{"title":"Lack of sumatriptan-induced aortic contraction or relaxation: 5-HT1B receptor protein detected in endothelium and smooth muscle of vasa vasorum but not aorta.","authors":"Marlene L Cohen, Elizabeth J Galbreath, Kathryn W Schenck, Danqing Li, Beth J Hoffman, Anindya Bhattacharya","doi":"","DOIUrl":"","url":null,"abstract":"Since 5-HT1B receptor mRNA was reported in rat aorta, and 5-HT1B receptor activation has been linked to vascular contraction, we explored sumatriptan-induced contractility and immunohistochemical density of 5-HT1B receptor protein in rat aorta. Sumatriptan (up to 10(-4) M), a 5-HT1B/1D receptor agonist, did not contract the endothelial intact or denuded rat aorta, even in the presence of L-NAME or after induction of modest tone with PGF2 alpha (10(-6) M). Sumatriptan also did not relax aortic preparations precontract with PGF2 alpha (3 x 10(-6) M) or phenylephrine (3 x 10(-7) M). Using a polyclonal antibody directed against the 5-HT1B receptor, minimal 5-HT1B receptor protein was detected in either the endothelium or smooth muscle of the rat aorta. However, dense 5-HT1B receptor protein was found in the vascular smooth muscle of the vasa vasorum supplying the aorta. Thus, the 5-HT1B receptor mRNA detected in tissue extracts of the rat aorta most likely reflects 5-HT1B receptor expression in the arterioles of the vasa vasorum. These studies support the link between the 5-HT1B receptor and vascular contraction in that the aorta with low density of 5-HT1B receptors lacked responses to sumatriptan, an agonist thought to contract blood vessels via 5-HT1B/1D receptors. Furthermore, caution must be observed when using 5-HT1B receptor mRNA to suggest receptor protein in tissues since this RT-PCR product may be derived predominantly from small blood vessels.","PeriodicalId":20928,"journal":{"name":"Receptors & channels","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22126323","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