氯通道阻断剂对α1-肾上腺素受体亚型引起的Ca2 +内流的影响

摘要

AIM　To investigate the roles of Cl- channels in C a2+ influx induced by activaion of α1-adrenoceptor subtypes in transfe cted-CHO cells.METHODS　The effects of drugs on α1A、α1 B and α1D-AR-induced Ca2+influx were investigated with Fura-2 fluorescence technique. RESULTS　The α1A-AR-induced Ca2 + influx was inhibited by furosemide（2.5～10 μmol·L-1）and SK&F96365 （5～15 μmol·L-1）in a concentration-dependent manner respectively；The α1B-AR-induced Ca2+ influx could also be inhibited by NFA（2.5 ～10 μmol·L-1），whereas the α1D-AR-induced Ca2+ influx w as only suppressed by NFA.In α1B-CHO cells，Adr-triggered Ca2+ in flux could be further inhibited by NFA or furosemide after the maximal inhibitio n by SK&F96365；SK&F96365 could further inhibit Ca2+ influx which had been inhibited by NFA or furosemide. In α1A-CHO cells，Adr-triggered Ca 2+ influx could be further inhibited by SK&F96365 after had been inhibited by furosemide； furosemide could not further inhibite Ca2+ influx which had b een inhibited by S&F96365. CONCLUSION　There are different character istics of Cl- channels related to α1A、 α1B and α1D-AR- induced Ca2+ influx.%目的探讨氯通道阻断剂在α1A、α1B、α1D 肾上腺素受体(AR)亚型触发的Ca2+ 内流中的作用。方法采用Fu ra- 2荧光探针双波长测定胞浆游离Ca2+浓度（［Ca2+］i）。结果在3种亚型的细胞上，肾上腺素(Adr)触发的Ca2+内流均不受nifedipine影响； SK&F9636 5可部分抑制α1A、α1B-AR介导的Ca2+内流，而对α1D-CHO细胞无影响。在α1B-CHO细胞上, niflumic acid（NFA）和furosemide呈浓度依赖性抑制Ca2+ 内流；当Ca2+ 内流被SK&F96365最大限度抑制后，NFA和furosemide 可进一步抑制Ca2+ 内流。α1A-AR介导的Ca2+内流可被furosemide抑制，抑制率达14%±5%。NFA可抑制α1D-AR引起的Ca2+内流，抑制率为39%±9 %。结论氯通道参与α1A、α1B及α1D-AR引起的经非电压依赖性Ca2+通道介导的Ca2+内流，其间存有异同。NFA敏感Ca2+ 内流及furosemide敏感的Ca2+ 内流与SK&F96365敏感的Ca2+内流存在非同一性。