Alpha 2 adrenoceptor potentiates glycine receptor-mediated taurine response through protein kinase A in rat substantia nigra neurons.
Alpha 2 adrenoceptor potentiates glycine receptor-mediated taurine response through protein kinase A in rat substantia nigra neurons.
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DOI：
10.1152/jn.1996.76.4.2447
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发表时间：
1996-10
影响因子：
2.5
通讯作者：
J. Nabekura;T. Omura;N. Akaike
中科院分区：
文献类型：
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作者：
J. Nabekura;T. Omura;N. Akaike
1. 在电压箝位条件下，采用制草素穿孔贴片记录模式研究了α - 2肾上腺素能受体对大鼠急性分离的黑质（SN）神经元的牛磺酸反应的调节作用。2. 在10(-3)M甘氨酸和3 × 10(-3) M牛磺酸诱导电流之间观察到完全的交叉脱敏。这两种电流均被10(-6)M士的宁拮抗，表明牛磺酸作用于SN神经元上对士的宁敏感的甘氨酸受体。3. 去甲肾上腺素（NE）与吡唑嗪（10(-5)M）和心得安（10(-5)M）同时应用，在保持电位（VH）为-40 mV时，以NE浓度依赖的方式增强牛磺酸反应（Itau）。可乐定模拟了NE对Itau的作用，从而表明α 2肾上腺素受体的激活参与了Itau的增强。α 2肾上腺素能被NE与吡唑嗪和心得安联合激活，显著增强了Itau的峰值幅度，但牛磺酸浓度-反应关系没有向左或向右移动。在10(-4)M NE与吡唑嗪（10(-5)M）和普萘洛尔（10(-5)M）存在时，阈值、半最大值和最大值的牛磺酸浓度分别为3 × 10(-5) M、3.1 × 10(-4) M和3 × 10(-3) M。在没有NE的情况下，牛磺酸浓度分别为3 × 10(-5) M、3.2 × 10(-4) M和3 × 10(-3) M。5. 有NE和没有NE的Itau的逆转电位都非常接近理论的Cl-平衡电位，这表明α - 2肾上腺素受体激活的Itau的增强是由于牛磺酸诱导的Cl-电流的增加。6. 福斯可林（3 × 10(-5) M）和异丁基甲基黄嘌呤（3 × 10(-5) M）抑制了Itau的峰值。当二丁基环AMP （10(-4) M）也抑制Itau时，α 2肾上腺素受体的激活不能增强Itau。N-[2（甲氨基）乙基]-5-异喹啉磺酰胺二盐酸盐（H-89）模拟α - 2肾上腺素受体对Itau的激活作用。此外，在10(-6)M H-89存在的情况下，没有观察到α 2肾上腺素受体对Itau的增强作用。8. 百日咳毒素（500 ng/ ml）作用SN神经元18 h后，α 2肾上腺素能受体对Itau的促进作用完全消失。上述结果提示，α 2肾上腺素能受体与iap敏感的GTP结合蛋白联用，可降低细胞内环AMP和环AMP依赖性蛋白激酶活性，从而增强大鼠SN神经元中甘氨酸受体介导的牛磺酸反应。
1. The modulatory effect of alpha 2 adrenoceptor on the taurine response was investigated in substantia nigra (SN) neurons acutely dissociated from the rat using a nystatin perforated-patch recording mode under voltage-clamp conditions. 2. Complete cross-desensitization was observed between 10(-3) M glycine and 3 x 10(-3) M taurine-induced currents. Both currents were antagonized by 10(-6) M strychnine, thus indicating that taurine acts on strychnine-sensitive glycine receptor on the SN neurons. 3. The simultaneous application of norepinephrine (NE) with prazosin (10(-5) M) and propranolol (10(-5) M) potentiated the taurine response (Itau) in an NE concentration-dependent manner at a holding potential (VH) of -40 mV. Clonidine mimicked the NE effect on the Itau, thus indicating the involvement of alpha 2 adrenoceptor activation in the potentiation of Itau. 4. Alpha 2 adrenoceptor activation by NE with prazosin and propranolol significantly potentiated the peak amplitude of Itau without shifting the taurine concentration-response relationships either to left or right side. The respective concentrations of taurine for the threshold, half maximal and maximal responses in the presence of 10(-4) M NE with prazosin (10(-5) M) and propranolol (10(-5) M) were 3 x 10(-5) M, 3.1 x 10(-4) M, and 3 x 10(-3) M. The same concentrations in the absence of NE were 3 x 10(-5) M, 3.2 x 10(-4) M, and 3 x 10(-3) M, respectively. 5. The reversal potentials of Itau with and without NE were very close to the theoretical Cl- equilibrium potential, thus indicating that the potentiation of Itau by alpha 2 adrenoceptor activation was due to an increase in the taurine-induced Cl- currents. 6. Forskolin (3 x 10(-5) M) and isobutylmethylxanthine (3 x 10(-5) M) suppressed the peak amplitude of Itau. In the presence of dibutyryl cyclic AMP (10(-4) M), which also suppressed Itau, alpha 2 adrenoceptor activation failed to potentiate Itau. 7. N-[2(methylamino)ethyl]-5-isoquinoline sulfonamide dihydrochloride (H-89) mimicked the effect of alpha 2 adrenoceptor activation on Itau. In addition, the potentiation of Itau by alpha 2 adrenoceptor was not observed in the presence of 10(-6) M H-89. 8. The treatment of SN neurons with pertussis toxin (500 ng/ ml) for 18 h completely abolished the facilitatory effect of alpha 2 adrenoceptor on Itau. 9. These results suggest that the activation of alpha 2 adrenoceptor coupled with IAP-sensitive GTP binding protein decreases the intracellular cyclic AMP and cyclic AMP-dependent protein kinase activity, thus resulting in the potentiation of glycine receptor-mediated taurine response in rat SN neurons.