Dimethyl sulfoxide: Inhibition of acetylcholinesterase in the mammalian heart

The heart rate of the isolated, perfused, working rat heart was significantly and equally depressed by 1 × 10 −6 M acetylcholine (ACh) and by 6 × 10 −5 M 4-ketoamyltrimethylammonium (4K), a cholinomimetic agonist. Dimethyl sulfoxide (DMSO) (10 μl/ml, 140 mM) strongly potentiated the effect of ACh but did not alter the effect of 4K. DMSO (10 μl/ml, 140 mM final concentration) alone had no significant effect upon heart rate when added to the perfusate in incremental additions of 1 μl · (ml perfusate) −1 · min −1 over a 10-min period. The specific activity of atrial homogenate cholinesterase was 48.8 ± 3.46 nmoles · min −1 · ( mg protein) −1 ( mean ± S.E.M.), 38.2 ± 1.60 for butyrylcholinesterase, and 11.2 ± 0.86 for acetylcholinesterase (AChE). True AChE activity (measured in the presence of a maximally effective concentration of tetraisopropylpyrophosphoramide) had a V max of 13.4 ± 0.17 nmoles · min −1 · (mg protein) −1 and an apparent K m value of 1 × 10 −4 M acetylthiocholine. At this K m substrate concentration, DMSO inhibited atrial AChE activity (I 50 = 9 μl/ml). At the concentration tested, DMSO inhibited atrial AChE and potentiated ACh effects.