Chergui K, Lacey M G
Department of Pharmacology, The Medical School, University of Birmingham, Edgbaston, UK.
Neuropharmacology. 1999 Feb;38(2):223-31. doi: 10.1016/s0028-3908(98)00187-7.
Dopamine, acting at a D1-like receptor, depresses the release of glutamate in the nucleus accumbens (NAcc) in brain slices, thereby reducing the amplitude of the excitatory postsynaptic current (EPSC). This effect depends upon an inhibitory feedback action of adenosine, liberated following facilitation of postsynaptic NMDA receptors by D1 receptor activation, an action independent of adenylyl cyclase stimulation or cyclic AMP-dependent protein kinase (PKA; Harvey, J., Lacey, M.G., 1997. J. Neurosci. 17, 5271). Using whole-cell recording from NAcc neurones, the dopamine depression of the EPSC was blocked by pre-treatment of brain slices with the selective protein kinase C (PKC) inhibitor Ro 32-0432, but only minimally attenuated by intracellular dialysis of single cells with Ro 32-0432 in the recording pipette. With synaptic transmission blocked by tetrodotoxin, inward currents caused by application of NMDA were enhanced by the D1 receptor agonist SKF 81297A in half the cells tested. In a separate population of cells dialysed intracellularly with Ro 32-0432, SKF 81297A was without effect on NMDA current amplitude. These findings indicate a functional role for phospholipase C-coupled D1-like receptors in both modulating synaptic transmission in NAcc and potentiating NMDA receptors on a subset of NAcc neurones, via PKC activation.
多巴胺作用于D1样受体，可抑制脑片伏隔核（NAcc）中谷氨酸的释放，从而降低兴奋性突触后电流（EPSC）的幅度。这种效应取决于腺苷的抑制性反馈作用，D1受体激活促进突触后NMDA受体后会释放腺苷，该作用独立于腺苷酸环化酶刺激或环磷酸腺苷依赖性蛋白激酶（PKA；哈维，J.，莱西，M.G.，1997年。《神经科学杂志》17，5271）。使用伏隔核神经元的全细胞记录，用选择性蛋白激酶C（PKC）抑制剂Ro 32 - 0432预处理脑片可阻断EPSC的多巴胺抑制作用，但在记录电极中用Ro 32 - 0432对单细胞进行细胞内透析时，其抑制作用仅略有减弱。用河豚毒素阻断突触传递后，在一半测试细胞中，D1受体激动剂SKF 81297A可增强应用NMDA所引起的内向电流。在另一组用Ro 32 - 0432进行细胞内透析的细胞中，SKF 81297A对NMDA电流幅度没有影响。这些发现表明，通过PKC激活，磷脂酶C偶联的D1样受体在调节伏隔核突触传递和增强一部分伏隔核神经元上的NMDA受体方面具有功能性作用。
