Receptors & channels最新文献

BacMam recombinant baculoviruses in G protein-coupled receptor drug discovery. 重组杆状病毒G蛋白偶联受体药物的发现。

Receptors & channels Pub Date : 2004-01-01 DOI: 10.1080/10606820490514969

Robert Ames, James Fornwald, Parvathi Nuthulaganti, John Trill, James Foley, Peter Buckley, Thomas Kost, Zining Wu, Michael Romanos

{"title":"BacMam recombinant baculoviruses in G protein-coupled receptor drug discovery.","authors":"Robert Ames, James Fornwald, Parvathi Nuthulaganti, John Trill, James Foley, Peter Buckley, Thomas Kost, Zining Wu, Michael Romanos","doi":"10.1080/10606820490514969","DOIUrl":"https://doi.org/10.1080/10606820490514969","url":null,"abstract":"With completion of the sequencing of the human and mouse genomes, the primary sequences of close to 400 non-olfactory G protein-coupled receptors (GPCRs) have been determined. There are intensive efforts within the pharmaceutical industry to discover and develop new therapeutic agents acting via GPCRs. In addition, there is a concerted effort to identify potential new drug targets from the remaining 150+orphan GPCRs through the identification of their ligands. Access to functionally expressed recombinant receptors underpins both of these key drug discovery activities. Typically, GPCR drug discovery screening activities are carried out using mammalian cell lines stably expressing the target of interest. The influx of new receptor sequences originating from genomic sequencing efforts has caused a shift toward wider applications of transient rather than stable expression systems, especially in support of assays for orphan receptor ligand screening. Recombinant baculoviruses in which the polyhedrin promoter has been replaced with a mammalian promoter, termed BacMam viruses, were originally designed as potential new gene therapy delivery vehicles. This same technology offers numerous advantages as a transient expression system in the assay of membrane-expressed drug targets, including GPCRs. Data presented show that BacMam can be used rapidly to generate robust and pharmacologically authentic GPCR assays in several formats, with the potential to transform drug discovery screening processes for this gene family.","PeriodicalId":20928,"journal":{"name":"Receptors & channels","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10606820490514969","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24787657","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: 57

Interactions of "ultra-low" doses of naltrexone and morphine in mature and young male and female rats. “超低”剂量纳曲酮和吗啡在成年和年轻雄性和雌性大鼠中的相互作用。

Receptors & channels Pub Date : 2004-01-01 DOI: 10.1080/10606820490464334

Scott R Hamann, Hammad Malik, Jewell W Sloan, Elzbieta P Wala

引用次数: 18

Proteinous amino acids in muscle cytosol of rats' heart, after their treatment with propranolol, pentylenetetrazol or reserpine. 心得安、戊四氮、利血平对大鼠心肌细胞质蛋白质氨基酸的影响。

Receptors & channels Pub Date : 2004-01-01 DOI: 10.1080/10606820490464343

Janusz Gabrys, Janusz Konecki, Maria Głowacka, Katarzyna Durczok, Katarzyna Sawczuk, Ryszard Brus, Grzegorz Bielaczyc, Przemysław Nowak, Jashovam Shani

{"title":"Proteinous amino acids in muscle cytosol of rats' heart, after their treatment with propranolol, pentylenetetrazol or reserpine.","authors":"Janusz Gabrys, Janusz Konecki, Maria Głowacka, Katarzyna Durczok, Katarzyna Sawczuk, Ryszard Brus, Grzegorz Bielaczyc, Przemysław Nowak, Jashovam Shani","doi":"10.1080/10606820490464343","DOIUrl":"https://doi.org/10.1080/10606820490464343","url":null,"abstract":"Tissue levels of nineteen amino acids and total free amino acids, were assayed by gas-liquid chromatography in cytosols of rat atrial and ventricular muscle cardiomyocytes. The tissues were assayed after the rats had been administered IP with the three cardioactive drugs, exerting a significant effect on their heart action: propranolol, pentylenetetrazol and reserpine. It was demonstrated that while in the atrial and ventricular cardiac muscle cytosols of control rats, arginine, glutamine and cysteine were detected in high levels (35.1% and 17.6%; 14.8% and 51.6%; 9.9% and 0.25% of the total free amino acids, respectively), all three drugs significantly reduced the total amounts of cytosolic free amino acids in both atrial and ventricular heart muscles. All three drugs (with reserpine in particular) modified the levels of arginine, cysteine, phenylalanine, tryptophan, isoleucine and tyrosine. The role of these amino acids in the heart muscle cytosol, and their involvement in the mechanism of action of these three cardioactive drugs, is discussed.","PeriodicalId":20928,"journal":{"name":"Receptors & channels","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/10606820490464343","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24571821","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

Comparison of the pharmacological properties of rat Na(V)1.8 with rat Na(V)1.2a and human Na(V)1.5 voltage-gated sodium channel subtypes using a membrane potential sensitive dye and FLIPR. 利用膜电位敏感染料和FLIPR比较大鼠Na(V)1.8与大鼠Na(V)1.2a和人Na(V)1.5电压门控钠通道亚型的药理学性质。

Receptors & channels Pub Date : 2004-01-01

R G Vickery, S M Amagasu, R Chang, N Mai, E Kaufman, J Martin, J Hembrador, M D O'Keefe, C Gee, D Marquess, J A M Smith

{"title":"Comparison of the pharmacological properties of rat Na(V)1.8 with rat Na(V)1.2a and human Na(V)1.5 voltage-gated sodium channel subtypes using a membrane potential sensitive dye and FLIPR.","authors":"R G Vickery, S M Amagasu, R Chang, N Mai, E Kaufman, J Martin, J Hembrador, M D O'Keefe, C Gee, D Marquess, J A M Smith","doi":"","DOIUrl":"","url":null,"abstract":"A novel, membrane potential sensitive dye and a fluorescence imaging plate reader (FLIPR) have been used to characterize the pharmacological properties of rat Na(v)1.8 voltage-gated sodium channels (VGSC) in parallel with rat Na(v)1.2a and human Na(v)1.5 VGSC subtypes, respectively. The sensitivity of recombinant Na(v)1.2a-CHO, Na(v)1.5-293-EBNA, and Na(v)1.8-F-11 cells to VGSC activators was subtype dependent. Veratridine evoked depolarization of Na(v)1.2a-CHO and Na(v)1.5-293-EBNA cells with pEC(50) values of 4.78 +/- 0.13 and 4.84 +/- 0.12, respectively (n = 3), but had negligible effect on Na(v)1.8-F-11 cells (pEC(50) < 4.5). Type I pyrethroids were without significant effect at all subtypes. In contrast, the type II pyrethroids deltamethrin and fenvalerate evoked direct depolarization of Na(v)1.8-F-11 and Na(v)1.5-293-EBNA cells. Deltamethrin potentiated the veratridine-evoked response in Na(v)1.8-F-11 cells by > or =20-fold, in contrast to a <or =3-fold potentiation of the response in Na(v)1.2a, and Na(v)1.5 cells. Tetrodotoxin (TTX) inhibited VGSC activator-evoked depolarization of Na(v)1.8-F-11 cells with a biphasic concentration-response curve. The calculated pIC(50) values were 8.05 +/- 0.25 (n = 4) and 4.32 +/- 0.21 (n = 4), corresponding to TTX inhibition of endogenous TTX-sensitive (TTX-S), and recombinant Na(v)1.8 TTX-resistant (TTX-R) VGSCs, respectively. With the exception of TTX, the potencies of a number of ion channel blockers for the Na(v)1.8, Na(v)1.2a, and Na(v)1.5 VGSC subtypes were similar. In summary, these high-throughput FLIPR assays represent a valuable tool for the determination of the relative potencies of compounds at different VGSC subtypes and may prove useful for the identification of novel subtype-selective inhibitors.","PeriodicalId":20928,"journal":{"name":"Receptors & channels","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24201825","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

Modification by L-NAME of codeine induced analgesia: possible role of nitric oxide. L-NAME修饰可待因诱导的镇痛:一氧化氮的可能作用。

Receptors & channels Pub Date : 2004-01-01 DOI: 10.3109/10606820490926098

Mahmoud M Khattab, Tarig M El-Hadiyah, Othman A Al-Shabanah, Muhammad Raza

{"title":"Modification by L-NAME of codeine induced analgesia: possible role of nitric oxide.","authors":"Mahmoud M Khattab, Tarig M El-Hadiyah, Othman A Al-Shabanah, Muhammad Raza","doi":"10.3109/10606820490926098","DOIUrl":"https://doi.org/10.3109/10606820490926098","url":null,"abstract":"Objectives were to investigate the effect of nonselective nitric oxide synthase (NOS) inhibitor, L-NAME on codeine-induced analgesia and to see the role of NO in its antinociceptive effect. Also, to see if L-NAME can potentiate the antinociceptive response of sub-effective dose of codeine and to explore if opioid receptors have some role to play in L-NAME effects. Mice were injected with selected doses of codeine or other selected agents intraperitoneally and the latency to hot plate was recorded at zero, 15, 30, and 60 min of the treatments. The antinociceptive response of codeine (10 mg/kg, i.p.) was studied in comparison to those of the NOS inhibitor, L-NAME, and of nitric oxide donor, sodium nitroprusside (SNP). Assessment of nitrates and nitrites (NOx) in the sera of treated mice were also made. Codeine (20 mg/kg dose), induced analgesia significantly and dose dependently only after 15 min. L-NAME at 20, 40, and 80 mg/kg dose levels significantly changed the nonanalgesic effect of codeine (10 mg/kg) to highly significant analgesia. The effect of L-NAME 40 mg/kg was significantly higher than the other two doses and was almost equal to that of the higher dose of codeine. Naloxone itself did not show any intrinsic effect but almost abolished the L-NAME-codeine induced analgesia. Similarly, SNP (1 mg/kg) reversed the decrease in reaction time by L-NAME-codeine to its control values, significantly. Pretreatment with L-NAME rendered the nonanalgesic dose of codeine significantly analgesic almost in an equal potency to the high dose of codeine alone and indicate that the NO modulatory effect on the opioid analgesic codeine is probably, at least in part, through opioid receptors.","PeriodicalId":20928,"journal":{"name":"Receptors & channels","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10606820490926098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25163447","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: 7

High efficiency activation of L-type Ca2+ current by 5-HT in human atrial myocytes. 5-HT对人心房肌细胞l型Ca2+电流的高效激活。

Receptors & channels Pub Date : 2004-01-01 DOI: 10.3109/10606820490926115

Emmanuella Di Scala, Ian Findlay, Stephanie Rose, Michel Aupart, Jorge Argibay, Pierre Cosnay, Veronique Bozon

引用次数: 5

Regulation of receptor-coupling to (multiple) G proteins. A challenge for basic research and drug discovery. 受体偶联到(多个)G蛋白的调控。对基础研究和药物发现的挑战。

Receptors & channels Pub Date : 2004-01-01 DOI: 10.3109/10606820490926151

Jyrki P Kukkonen

引用次数: 37

G-protein coupled receptors as allosteric machines. 作为变构机制的g蛋白偶联受体。

Receptors & channels Pub Date : 2004-01-01 DOI: 10.1080/10606820490464316

Terry Kenakin