I have been working on aquaporins and literaturre says merrcury inhibits AQPs. Few published articles say Thrombin, TPA, bumetadine, Propofol pholoretin etc..
CAn someone suggest me the best among there or other copounds with your experience that it inhibits aquaporin
Sorry, I can not help you, I do not use inhibitors of AQPs in my research. How about that you ask Dr. Alan Verkman in San Francisco ([email protected]). $
Dear Arun,
A novel blocker of mammalian aquaporin channels, AqB013, is more effective than mercury at the same dose (50 µM), as illustrated here for mammalian AQP1 channels in the Xenopus oocyte expression system. Oocytes were placed into 50% hypotonic saline at time zero. Data are mean ± SD, for 10 oocytes per treatment, with swelling
rates calculated from the change in cross-sectional area as a function of time using video imaging. Control oocytes lack AQP channel expression and show minimal swelling in hypotonic conditions.
For more information, see attached file.
Hoping this will be helpful,
Rafik
Dear Rafik
Thanks for your reply. I saw that article it was bumetanide derivative. On top it was mentioned that it was given intra cellularly to oocytes. I was wondering if it would inhibit all other isoforms too
Thanks
Arun
Dear Arun,
I think it will.
I have copied a paragraph from the following publication which gives some short overview on this kind of inhibitors. It may interest you:
Inhibitors of aquaporins with translational potential are needed. Blockers found thus far are handicapped by toxicity, low efficacy, and lack of specificity. Mercurials block certain classes such as AQP1 (Preston et al., 1993) but not AQP4 (Jung et al., 1994a), but toxicity limits therapeutic value. Antiepileptic compounds (Huber et al., 2009), acetazolamide (Ma et al., 2004), and metal ions (Niemietz and Tyerman, 2002) also have been proposed as AQP inhibitors. The nonmercurial AQP1 blocker, tetraethylammonium ion (TEA+), decreases AQP1-mediated water fluxes in the oocyte expression system (Brooks et al., 2000; Detmers et al., 2006) and in the kidney (Yool et al., 2002). TEA block of AQPs is supported by molecular dynamic modeling (Muller et al., 2008), although is not seen in all assays (Yang et al., 2006). TEA also blocks a variety of K+ channels and other membrane proteins.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2701455/
The following article may provide some important information regarding the topic of your question:
Targeting Aquaporin Function: Potent Inhibition of Aquaglyceroporin-3 by a Gold-Based Compound
Ana Paula Martins , Alessandro Marrone , Antonella Ciancetta , Ana Galán Cobo , Miriam Echevarría , Teresa F. Moura , Nazzareno Re , Angela Casini , Graça Soveral
Published: May 18, 2012DOI: 10.1371/journal.pone.0037435
Abstract
Aquaporins (AQPs) are membrane channels that conduct water and small solutes such as glycerol and are involved in many physiological functions. Aquaporin-based modulator drugs are predicted to be of broad potential utility in the treatment of several diseases. Until today few AQP inhibitors have been described as suitable candidates for clinical development. Here we report on the potent inhibition of AQP3 channels by gold(III) complexes screened on human red blood cells (hRBC) and AQP3-transfected PC12 cells by a stopped-flow method. Among the various metal compounds tested, Auphen is the most active on AQP3 (IC50 = 0.8±0.08 µM in hRBC). Interestingly, the compound poorly affects the water permeability of AQP1. The mechanism of gold inhibition is related to the ability of Au(III) to interact with sulphydryls groups of proteins such as the thiolates of cysteine residues. Additional DFT and modeling studies on possible gold compound/AQP adducts provide a tentative description of the system at a molecular level. The mapping of the periplasmic surface of an homology model of human AQP3 evidenced the thiol group of Cys40 as a likely candidate for binding to gold(III) complexes. Moreover, the investigation of non-covalent binding of Au complexes by docking approaches revealed their preferential binding to AQP3 with respect to AQP1. The high selectivity and low concentration dependent inhibitory effect of Auphen (in the nanomolar range) together with its high water solubility makes the compound a suitable drug lead for future in vivo studies. These results may present novel metal-based scaffolds for AQP drug development.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0037435
Rafik
Dear Rafik
Thanks for your reply. Your ideas gave me a clarity. I would start off my experiments with inhibition in animals.
Dear Arun,
That question is a bit tricky as mercury is the only inhibitor that works for all (or most) aquaporins. Are you looking to reduce AQP expression or to inhibit function? And in which isoforms are you interested in?
Our recent work has been focused mainly on gold complexes on aquaglyceroporin inhibitors (You can have an overview here: https://www.researchgate.net/publication/264315469_Gold_compounds_as_aquaporin_inhibitors_New_opportunities_for_therapy_and_imaging?ev=prf_pub).
Article Gold compounds as aquaporin inhibitors: New opportunities fo...
Hi Anderia
Thanks for your reply. Its like aquaporin expression is increased in my condition so i need to prove that all the downstream process effect is due to aquaporins so it would be efficient if i inhibit aquaporin rather even reducing aquaporin expression will help . will go through your publication and in case of any doubts would contact you...
Thanks in advance....
Dear Arun,
No problem. If ou have any questions, fell free to contact me via ResearchGate or directly by email ([email protected]).
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