Fukunaga Izumi, Yeo Christopher H, Batchelor Andrew M
Departments of Physiology and Anatomy, University College London, Gower Street, London WC1E 6BT, UK.
Neuropharmacology. 2007 Feb;52(2):450-8. doi: 10.1016/j.neuropharm.2006.08.014. Epub 2006 Oct 10.
CPCCOEt (7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester) is frequently used to test for the involvement of mGlu1 receptors. Using whole-cell voltage recording from Purkinje cells in slices of rat cerebellum we find that CPCCOEt, at concentrations used to block mGlu1 receptors, causes an enhancement of the climbing fibre response. Application of alternative antagonists with activity at mGlu1 neither mimicked nor occluded the effects of CPCCOEt. Receptor antagonists demonstrated that this non-mGlu1 action of CPCCOEt was not mediated by other mGlu receptors or GABA(B) receptors. Voltage-clamped climbing fibre EPSCs are unaffected by CPCCOEt whilst application of a glutamate transport blocker did not occlude the CPCCOEt effect. This suggests that a postsynaptic voltage-dependent component of the complex climbing fibre response is the target. We have found no evidence for the involvement of the hyperpolarisation-activated current, I(h), and calcium-activated conductances. Voltage-gated sodium, calcium and potassium channels are possible targets with inhibition of a potassium channel the most likely. Awareness of this non-mGlu-mediated effect of CPCCOEt is likely to be important for the correct interpretation of its actions.
CPCCOEt（7-（羟基亚氨基）环丙并[b]色烯-1a-羧酸乙酯）常用于检测代谢型谷氨酸受体1（mGlu1）的参与情况。利用大鼠小脑切片中浦肯野细胞的全细胞电压记录，我们发现，在用于阻断mGlu1受体的浓度下，CPCCOEt会增强攀缘纤维反应。应用对mGlu1有活性的其他拮抗剂既不能模拟也不能阻断CPCCOEt的作用。受体拮抗剂表明，CPCCOEt的这种非mGlu1作用不是由其他mGlu受体或γ-氨基丁酸B（GABA(B)）受体介导的。电压钳制的攀缘纤维兴奋性突触后电流不受CPCCOEt影响，而应用谷氨酸转运体阻滞剂并不能阻断CPCCOEt的作用。这表明复杂攀缘纤维反应的突触后电压依赖性成分是靶点。我们没有发现超极化激活电流I(h)和钙激活电导参与其中的证据。电压门控钠通道、钙通道和钾通道可能是靶点，其中抑制钾通道的可能性最大。认识到CPCCOEt的这种非mGlu介导的作用可能对正确解释其作用很重要。
