Guanidinoethyl sulphonate is a glycine receptor antagonist in striatum

Guanidinoethyl sulphonate (GES) is an analogue of taurine and an inhibitor of taurine transport. Interactions of GES with GABAA and glycine receptors are studied by whole cell recording and fast drug application in isolated striatal neurons of the mouse. We confirm that GES is a weak agonist at GABAA receptors, and is able to antagonize GABA‐evoked responses. GES did not gate GlyR. GES antagonized glycine responses in a concentration‐dependent and surmountable manner. Glycine dose–response curves were shifted to the right by GES (0.5 mM), yielding EC50s and Hill coefficients of 62 μM and 2.5 in control, 154 μM and 1.3 in the presence of GES. GlyR‐mediated taurine responses were competitively antagonized by GES. Taurine dose–response curves, in contrast to the glycine dose–response curves were shifted by GES to the right in a parallel manner. The GlyR‐block by GES was not voltage‐dependent. In contrast to our findings in the mouse, in rat striatal neurons which lack expression of the α3 GlyR subunit, GES shifted the glycine dose–response curve to the right in a parallel way without affecting the maximal response. Subtype‐specificity of the GES action at GlyR must await further investigation in artificial expression systems. We conclude that GES is a competitive antagonist at GlyR. The antagonistic action of GES at inhibitory ionotropic receptors can explain its epileptogenic action. Care must be taken with the interpretation of data on GES evoked taurine release.