Hello, I want to ask a question regarding the inhibitory action of DMSO with AChe. If DMSO are showing inhibitory activity against AChE, and we supplied drug by using DMSO as a vehicle. Then how we decide the inhibitory activities shown for AChE is by a drug or by DMSO. What are the important criteria by which we differentiate the inhibitory action between two.
The effects of the solution containing 0.5% of DMSO on the arterial smooth muscle (rat aortal rings in vitro) is a minimal relaxation - up to 5% of the tone elicited - precontracted by low concentration of phenylephrine (EC30 concentration). The effects may be NO mediated or some other mechanisms? I did not test for mechanisms but the very high concentration of DMSO may indicate nonspecific effect. I recommend using 10 or 100 times less concentrated DMSO solutions and doing, IN PARALEL, the tests with the control solutions (as Christopher suggested).
I would recommend testing with the DMSO vehicle minus the drug, to see what response you get. Despite being a competitive inhibitor, concentrations of just DMSO may potentiate ACh transmission as well as inhibit AChE activity. May I ask which drug you are using?
Thanks for your quick response Christopher. I am using Quercetin as a drug candidate.
The effects of the solution containing 0.5% of DMSO on the arterial smooth muscle (rat aortal rings in vitro) is a minimal relaxation - up to 5% of the tone elicited - precontracted by low concentration of phenylephrine (EC30 concentration). The effects may be NO mediated or some other mechanisms? I did not test for mechanisms but the very high concentration of DMSO may indicate nonspecific effect. I recommend using 10 or 100 times less concentrated DMSO solutions and doing, IN PARALEL, the tests with the control solutions (as Christopher suggested).
Inhibition of acetylcholinesterase of mice erythrocytes & synaptosomes by dimethylsulfoxide.
Jagota SK1.
Abstract
In vitro inhibitory effect of dimethylsulfoxide (DMSO) on acetylcholinesterase of erythrocyte membranes and synaptosomes of mice was observed using acetylthiocholine as substrate. DMSO inhibited the enzyme from both sources and the effect was concentration dependent. It produced an inhibition of 26 to 28 per cent at a concentration of 0.13 mM and 92 to 95 per cent at a higher concentration of 1.91 mM. The Km of bound and solubilized enzyme of the synaptosomes was 0.2 and 0.15 mM while that of erythrocyte membranes 0.5 and 0.33 mM respectively. The Vmax was 0.4 and 0.4 (for synaptosomes) and 0.67 and 0.59 (for erythrocyte membranes) Mmoles/mg protein/min, respectively for bound and solubilized forms. The Ki of solubilized enzyme of synaptosomes was 0.11 mM. Kinetic studies showed that the inhibition was competitive in nature.
http://www.ncbi.nlm.nih.gov/pubmed/1459669
The mM concentration may be already quite relevant. Although we found that AchE pathway probably is not so directly important for tension control in vascular tissue (see the second part of the ATTACHED article). The hopes of use of DMSO as therapy failed, but theoretical importance may be still there. For the use as a solvent in in vitro experiments, the low concentrations should be taken and certainly the control experiments will always be needed.
As a control, you should do the experiments with DMSO alone.
I have faced the same problem in my experiments with plant extracts, and the DMSO spoiled some experiments.
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