Min B I, Kim C J, Rhee J S, Akaike N
Department of Physiology, College of Medicine, Kyung Hee University, Tongdaemoon-Gu, Seoul, South Korea.
Brain Res. 1996 Sep 23;734(1-2):72-8.
Effect of a mu-opioid agonist (D-Ala2,N-MePhe4,Gly5-ol-enkephalin, DAGO), on glycine (Gly)-induced chloride current (IGly) was investigated in the periaqueductal gray (PAG) neurons acutely dissociated 1-2-week-old Wistar rats by the use of nystatin-perforated patch recording configuration under voltage-clamp condition. At a holding potential (VH) of -40 mV, DAGO caused a sustained potentiation of IGly at the low concentrations (10(-6)-10(-5) M) but reduced slightly the Gly response at the high concentration (10(-4) M). The reversal potential of IGly was equal to the Cl- equilibrium potential (ECl) and was not changed in the presence of 10(-6) M DAGO. The 10(-5) M Gly response was inhibited by the simultaneous treatment of forskolin and 3-isobutyl-1-methylxanthine (IBMX). H-89, a protein kinase A (PKA) inhibitor, increased the 10(-5) M Gly response but had little effect on the 10(-4) M Gly response. DAGO increased 10(-5) M Gly response in the presence of forskolin and IBMX but, not more than in the absence of forskolin and IBMX. The 10(-5) M Gly response augumented by DAGO was not affected by adding H-89. The present results suggest that the glycine-induced chloride current is cAMP dependent and is inhibited by PKA, and that the potentiation of the glycine response by DAGO is also cAMP dependent and is due to the inhibition of PKA as that of H-89. We conclude that the potentiation of glycine response by DAGO is mediated by an inhibition of cAMP-dependent PKA in the PAG neurons.
在电压钳制条件下，采用制霉菌素穿孔膜片钳记录模式，研究了μ阿片受体激动剂（D-丙氨酸2，N-甲基苯丙氨酸4，甘氨酸5-脑啡肽，DAGO）对急性分离的1-2周龄Wistar大鼠中脑导水管周围灰质（PAG）神经元甘氨酸（Gly）诱导的氯离子电流（IGly）的影响。在-40 mV的钳制电位（VH）下，低浓度（10（-6）-10（-5）M）的DAGO可使IGly持续增强，但高浓度（10（-4）M）时则使Gly反应略有降低。IGly的反转电位等于氯离子平衡电位（ECl），且在存在10（-6）M DAGO时不变。10（-5）M Gly反应受到福斯可林和3-异丁基-1-甲基黄嘌呤（IBMX）同时处理的抑制。蛋白激酶A（PKA）抑制剂H-89增加了10（-5）M Gly反应，但对10（-4）M Gly反应影响很小。在存在福斯可林和IBMX的情况下，DAGO增加了10（-5）M Gly反应，但增加幅度不超过不存在福斯可林和IBMX时。DAGO增强的10（-5）M Gly反应不受添加H-89的影响。目前的结果表明，甘氨酸诱导的氯离子电流是cAMP依赖性的，且受PKA抑制，DAGO对甘氨酸反应的增强也是cAMP依赖性的，并且与H-89一样是由于PKA的抑制。我们得出结论，DAGO对甘氨酸反应的增强是通过抑制PAG神经元中cAMP依赖性PKA介导的。
