Receptors & channels最新文献_第9页

Microstructured apertures in planar glass substrates for ion channel research. 平面玻璃基板微结构孔径离子通道研究。

Receptors & channels Pub Date : 2003-01-01 DOI: 10.1080/10606820308256

N. Fertig, M. George, M. Klau, C. Meyer, A. Tilke, C. Sobotta, R. Blick, J. Behrends

引用次数: 56

Structure/activity relationships of M2 muscarinic allosteric modulators. M2毒蕈碱变构调节剂的构效关系。

Receptors & channels Pub Date : 2003-01-01 DOI: 10.3109/10606820308264

K. Mohr, C. Tränkle, U. Holzgrabe

引用次数: 36

High throughput electrophysiology: new perspectives for ion channel drug discovery. 高通量电生理学:离子通道药物发现的新视角。

Receptors & channels Pub Date : 2003-01-01 DOI: 10.3109/10606820308259

N. Willumsen, M. Bech, S. Olesen, B. Jensen, Mads P. G. Korsgaard, P. Christophersen

{"title":"High throughput electrophysiology: new perspectives for ion channel drug discovery.","authors":"N. Willumsen, M. Bech, S. Olesen, B. Jensen, Mads P. G. Korsgaard, P. Christophersen","doi":"10.3109/10606820308259","DOIUrl":"https://doi.org/10.3109/10606820308259","url":null,"abstract":"Proper function of ion channels is crucial for all living cells. Ion channel dysfunction may lead to a number of diseases, so-called channelopathies, and a number of common diseases, including epilepsy, arrhythmia, and type II diabetes, are primarily treated by drugs that modulate ion channels. A cornerstone in current drug discovery is high throughput screening assays which allow examination of the activity of specific ion channels though only to a limited extent. Conventional patch clamp remains the sole technique with sufficiently high time resolution and sensitivity required for precise and direct characterization of ion channel properties. However, patch clamp is a slow, labor-intensive, and thus expensive, technique. New techniques combining the reliability and high information content of patch clamping with the virtues of high throughput philosophy are emerging and predicted to make a number of ion channel targets accessible for drug screening. Specifically, genuine HTS parallel processing techniques based on arrays of planar silicon chips are being developed, but also lower throughput sequential techniques may be of value in compound screening, lead optimization, and safety screening. The introduction of new powerful HTS electrophysiological techniques is predicted to cause a revolution in ion channel drug discovery.","PeriodicalId":20928,"journal":{"name":"Receptors & channels","volume":"66 1","pages":"3-12"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88876552","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: 51

Introduction: an evolution of electrophysiology. 导言:电生理学的进化。

Receptors & channels Pub Date : 2003-01-01 DOI: 10.1080/10606820308255

Worley J rd

引用次数: 2

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

Katrin Schnizler, Mike Küster, Christoph Methfessel, Michael Fejtl

{"title":"The roboocyte: automated cDNA/mRNA injection and subsequent TEVC recording on Xenopus oocytes in 96-well microtiter plates.","authors":"Katrin Schnizler, Mike Küster, Christoph Methfessel, Michael Fejtl","doi":"","DOIUrl":"","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":"9 1","pages":"41-8"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22453419","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

Unaltered agonist potency upon inducible 5-HT7(a) but not 5-HT4(b) receptor expression indicates agonist-independent association of 5-HT7(a) receptor and Gs. 激动剂对诱导的5-HT7(a)而不是5-HT4(b)受体表达的效力不变，表明5-HT7(a)受体与Gs的关联不依赖于激动剂。

Receptors & channels Pub Date : 2003-01-01

Skjalg Bruheim, Kurt A Krobert, Kjetil Wessel Andressen, Finn Olav Levy

{"title":"Unaltered agonist potency upon inducible 5-HT7(a) but not 5-HT4(b) receptor expression indicates agonist-independent association of 5-HT7(a) receptor and Gs.","authors":"Skjalg Bruheim, Kurt A Krobert, Kjetil Wessel Andressen, Finn Olav Levy","doi":"","DOIUrl":"","url":null,"abstract":"We compared adenylyl cyclase (AC) activation by the G protein-coupled human serotonin (5-HT) receptors 5-HT4(b) and 5-HT7(a) using an ecdysone-inducible expression system, which allowed for reproducible expression of increasing receptor densities in clonal HEK293 (EcR293) cell lines. Low constitutive expression of receptors (2-70 fmol/mg protein) was observed and could be titrated up to 50-200-fold (approximately 400-7000 fmol/mg protein) by the ecdysone analogue ponasterone A. Although 5-HT-stimulated AC activity increased with receptor density, interclonal variation precluded comparisons of coupling efficiency. Interestingly, the potency of 5-HT to stimulate AC increased with increasing receptor density only in clones expressing 5-HT4(b) receptors. The potency for 5-HT did not change in clones expressing 5-HT7(a) receptors, even though 5-HT-stimulated AC activity approached asymptotic levels. This indicates that potency of 5-HT for stimulation of AC through the 5-HT7(a) receptor is independent of receptor-Gs stoichiometry and is consistent with a model where the 5-HT7(a) receptors are tightly associated with G protein, independent of agonist binding. This supports the existence of a complex between inactive receptor and G protein, as predicted by the cubic ternary complex model. In such a system, spare receptors do not lead to increased potency of an agonist with increased receptor density.","PeriodicalId":20928,"journal":{"name":"Receptors & channels","volume":"9 2","pages":"107-16"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22529267","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

Joe B Blumer, Stephen M Lanier

引用次数: 0

Effects of (+/-)-idazoxan alone and in combination with L-DOPA methyl ester in MPTP-induced hemiparkinsonian monkeys. (+/-)-咪唑嗪单用及联用左旋多巴甲酯对mptp诱导的偏帕金森猴的影响。

Receptors & channels Pub Date : 2003-01-01 DOI: 10.3109/713745180

Edward F Domino, Lisong Ni, Francis Colpaert, Marc Marien

引用次数: 17

Biogenic amines in striatum of rats that had been treated with ethanol, and their brains later stored in different temperatures. 用乙醇处理的大鼠纹状体中的生物胺，然后将它们的大脑储存在不同的温度下。

Receptors & channels Pub Date : 2003-01-01 DOI: 10.3109/713745172

Przemyslaw Nowak, Lukasz Labus, Joanna Stabryla, Artur Durczok, Ryszard Brus, Joanna Nowicka, Jashovam Shani

{"title":"Biogenic amines in striatum of rats that had been treated with ethanol, and their brains later stored in different temperatures.","authors":"Przemyslaw Nowak, Lukasz Labus, Joanna Stabryla, Artur Durczok, Ryszard Brus, Joanna Nowicka, Jashovam Shani","doi":"10.3109/713745172","DOIUrl":"https://doi.org/10.3109/713745172","url":null,"abstract":"The purpose of this study was to investigate how ethanol pretreatment and storage temperatures of brain striatum affect levels of biogenic amines in this tissue. Adult Wistar male rats were injected with 25% ethanol (5.0 g/kg i.p.) while the control rats were administered i.p. with the same volume of saline. Two hours later the rats were decapitated, their brains removed, and the striatum separated. Each striatum was divided into three parts: one part was immediately frozen on dry ice and kept at -70 degrees C; a second fragment was kept in a household refrigerator (+4 degrees C); and the third fragment was kept at +22 degrees C. Twenty-four hours later, levels of DA, DOPAC, HVA, 3-MT, 5-HT, and 5-HIAA in the striatum were assayed by HPLC/ED. Immediately after decapitation; ethanol levels were assayed in the serum of ethanol-pretreated and saline-pretreated rats using gas chromatography. Our results indicate that levels of striatal DA, DOPAC, and HVA in saline-pretreated rats decreased significantly when the storage temperature of the striatum was raised from -70 degrees C, through +4 degrees C, to +22 degrees C, while levels of striatal 5-HT and 5-HIAA remained constant within the temperature range tested and levels of 3-MT fluctuated. In ethanol-pretreated rats, striatal levels of DOPAC, HVA, and 5-HIAA were increased in all three storage temperatures, while levels of DA, 5-HT, and 3-MT were decreased in those temperatures. Those decreases were most profound in striatal samples kept at +22 degrees C. We conclude that concern about possible interactions between drugs and biogenic amines should be exercised.","PeriodicalId":20928,"journal":{"name":"Receptors & channels","volume":"9 5","pages":"339-42"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/713745172","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24014306","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: 4

Melatonin for the treatment of disorders in circadian rhythm and sleep: could it form a basis for medication? 褪黑素用于治疗昼夜节律和睡眠障碍:它能成为药物治疗的基础吗?

Receptors & channels Pub Date : 2003-01-01 DOI: 10.3109/714041018

Isaac Nir

引用次数: 9