Competitive inhibition by dimethylsulfoxide of molluscan and vertebrate acetylcholinesterase

Abstract

Anticholinesterase-like effects of dimethylsulfoxide (DMSO) were demonstrated on a variety of invertebrate muscles. The excitatory effects of acetylcholine (ACh) on the isolated preparations of the Geukensia demissa heart and anterior byssus retractor muscle (ABRM), and of the Busycon contrarium radula protractor muscle, were potentiated by DMSO (1–5 μl/ml; 1 μl/ml; = 14 mM). The negative chronotropic effects of ACh, but not of 4-ketoamyltrimethylammonium, were potentiated by DMSO (1–5 μl/ml) on the isolated heart of the oyster Crassostrea virginica. These four muscles have acetylcholinesterase enzymes of high activity. In contrast, Mercenaria mercenaria hearts have weak cholinesterase activity, and the effects of ACh on this isolated myocardium were not potentiated by DMSO (2–20 μl/ml). DMSO (0.1–15 μl/ml) was a competitive inhibitor of both a crude preparation of oyster heart acetylcholinesterase (AChE) (the K m increased 24-fold with DMSO at 15 μl/ml; the I 50 was 1.3 μl/ml DMSO when [ACh] = K m ) and a purified Electrophorus AChE (the Km increased 4.5-fold when DMSO was 10 μl/ml; the I 50 was 10 μl/ml DMSO near [ACh] = K m ). The same doses of DMSO were needed to potentiate the pharmacological effects of ACh on the oyster heart, as to inhibit the AChE of this tissue.