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991.
Huma Saleem Stephen C Tovey Tedeusz F Molinski Colin W Taylor 《British journal of pharmacology》2014,171(13):3298-3312
BACKGROUND AND PURPOSE
Inositol 1,4,5-trisphosphate receptors (IP3Rs) are intracellular Ca2+ channels. Interactions of the commonly used antagonists of IP3Rs with IP3R subtypes are poorly understood.EXPERIMENTAL APPROACH
IP3-evoked Ca2+ release from permeabilized DT40 cells stably expressing single subtypes of mammalian IP3R was measured using a luminal Ca2+ indicator. The effects of commonly used antagonists on IP3-evoked Ca2+ release and 3H-IP3 binding were characterized.KEY RESULTS
Functional analyses showed that heparin was a competitive antagonist of all IP3R subtypes with different affinities for each (IP3R3 > IP3R1 ≥ IP3R2). This sequence did not match the affinities for heparin binding to the isolated N-terminal from each IP3R subtype. 2-aminoethoxydiphenyl borate (2-APB) and high concentrations of caffeine selectively inhibited IP3R1 without affecting IP3 binding. Neither Xestospongin C nor Xestospongin D effectively inhibited IP3-evoked Ca2+ release via any IP3R subtype.CONCLUSIONS AND IMPLICATIONS
Heparin competes with IP3, but its access to the IP3-binding core is substantially hindered by additional IP3R residues. These interactions may contribute to its modest selectivity for IP3R3. Practicable concentrations of caffeine and 2-APB inhibit only IP3R1. Xestospongins do not appear to be effective antagonists of IP3Rs. 相似文献992.
993.
Anne Raben PhD Pia Siig Vestentoft PhD Jennie Brand-Miller PhD Elli Jalo MSc Mathjis Drummen PhD Liz Simpson PhD J. Alfredo Martinez PhD Teodora Handjieva-Darlenska PhD Gareth Stratton PhD Maija Huttunen-Lenz PhD Tony Lam MBA Jouko Sundvall MSc Roslyn Muirhead PhD Sally Poppitt PhD Christian Ritz PhD Kirsi H. Pietiläinen PhD Margriet Westerterp-Plantenga PhD Moira A. Taylor PhD Santiago Navas-Carretero PhD Svetoslav Handjiev PhD Melitta A. McNarry PhD Sylvia Hansen MSc Laura Råman BSc Shannon Brodie MSc Marta P. Silvestre PhD Tanja C. Adam PhD Ian A. Macdonald PhD Rodrigo San-Cristobal PhD Nadka Boyadjieva PhD Kelly A. Mackintosh PhD Wolfgang Schlicht PhD Amy Liu PhD Thomas M. Larsen PhD Mikael Fogelholm DSc 《Diabetes, obesity & metabolism》2021,23(2):324-337
994.
995.
Synthesis,characterization, and monoamine transporter activity of the new psychoactive substance 3′,4′‐methylenedioxy‐4‐methylaminorex (MDMAR) 下载免费PDF全文
Gavin McLaughlin Noreen Morris Pierce V. Kavanagh John D. Power Brendan Twamley John O'Brien Brian Talbot Geraldine Dowling Olivia Mahony Simon D. Brandt Julian Patrick Roland P. Archer John S. Partilla Michael H. Baumann 《Drug testing and analysis》2015,7(7):555-564
The recent occurrence of deaths associated with the psychostimulant cis‐4,4′‐dimethylaminorex (4,4′‐DMAR) in Europe indicated the presence of a newly emerged psychoactive substance on the market. Subsequently, the existence of 3,4‐methylenedioxy‐4‐methylaminorex (MDMAR) has come to the authors' attention and this study describes the synthesis of cis‐ and trans‐MDMAR followed by extensive characterization by chromatographic, spectroscopic, mass spectrometric platforms and crystal structure analysis. MDMAR obtained from an online vendor was subsequently identified as predominantly the cis‐isomer (90%). Exposure of the cis‐isomer to the mobile phase conditions (acetonitrile/water 1:1 with 0.1% formic acid) employed for high performance liquid chromatography analysis showed an artificially induced conversion to the trans‐isomer, which was not observed when characterized by gas chromatography. Monoamine release activities of both MDMAR isomers were compared with the non‐selective monoamine releasing agent (+)‐3,4‐methylenedioxymethamphetamine (MDMA) as a standard reference compound. For additional comparison, both cis‐ and trans‐4,4′‐DMAR, were assessed under identical conditions. cis‐MDMAR, trans‐MDMAR, cis‐4,4′‐DMAR and trans‐4,4′‐DMAR were more potent than MDMA in their ability to function as efficacious substrate‐type releasers at the dopamine (DAT) and norepinephrine (NET) transporters in rat brain tissue. While cis‐4,4′‐DMAR, cis‐MDMAR and trans‐MDMAR were fully efficacious releasing agents at the serotonin transporter (SERT), trans‐4,4′‐DMAR acted as a fully efficacious uptake blocker. Currently, little information is available about the presence of MDMAR on the market but the high potency of ring‐substituted methylaminorex analogues at all three monoamine transporters investigated here might be relevant when assessing the potential for serious side‐effects after high dose exposure. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
996.
Navin Patrick J. Kim Bohyun Wells Michael L. Khandelwal Ashish Halaweish Ahmed F. Moen Taylor R. Johnson Matthew P. McCollough Shannon Lee Yong Suk Leng Shuai McCollough Cynthia H. Fletcher Joel G. 《Abdominal imaging》2019,44(10):3350-3358
Abdominal Radiology - Prior iterative reconstruction (PIR) uses spatial information from one phase of enhancement to reduce image noise in other phases. We sought to determine if PIR could reduce... 相似文献
997.
Frederick R. Taylor MD FAAN FAHS Wade M. Cooper DO Robert G. Kaniecki MD 《Headache》2019,59(8):1407-1418
998.
999.
Pierre Ct Hainan Yu Heather M. Shearer Kristi Randhawa Jessica J. Wong Silvano Mior Arthur Ameis Linda J. Carroll Margareta Nordin Sharanya Varatharajan Deborah Sutton Danielle Southerst Craig Jacobs Maja Stupar Anne Taylor‐Vaisey Douglas P. Gross Robert J. Brison Mike Paulden Carlo Ammendolia J. David Cassidy Patrick Loisel Shawn Marshall Richard N. Bohay John Stapleton Michel Lacerte 《European Journal of Pain》2019,23(6):1051-1070