Franck H, Storr M, Puschmann A, Schusdziarra V, Allescher H D
Department of Internal Medicine II, Technical University of Munich, 81675 Munich, Germany.
Am J Physiol. 1998 Jul;275(1):G159-68. doi: 10.1152/ajpgi.1998.275.1.G159.
We investigated the role of K+ channels and intracellular Ca2+ stores in the relaxations induced by the NO donor 3-morpholinosydnonimine (SIN-1) and 8-bromo-cGMP (8-BrcGMP), 8-(4-chlorophenylthio)-cGMP (pCPT-cGMP), and alpha, beta-methylene-ATP in isolated segments of rat ileum. The inhibitory responses to SIN-1 and the cGMP analogs were not influenced by the K+ blockers apamin, charybdotoxin, iberiotoxin, or glibenclamide, whereas relaxations induced by alpha,beta-methylene-ATP were abolished by apamin and tetraethylammonium. The NO-donor SIN-1 and the cGMP analogs were able to inhibit contractions induced by activation of L-type Ca2+ channels (BAY-K-8644), by carbachol (CCh), and by cyclopiazonic acid (CPA), a blocker of sarcoplasmic Ca2+-ATPase. However, the inhibition of the combined CPA and CCh response was reduced and the dose-response curve of SIN-1 shifted to the right. Intracellular Ca2+ stores were emptied by incubation in Ca2+-free buffer and repetitive stimulation with CCh or BAY-K-8644. After restoration of extracellular Ca2+, the inhibitory effect of SIN-1 and pCPT-cGMP was only attenuated, whereas in the additional presence of CPA, the inhibitory effect of SIN-1 was blocked and the effect of 8-BrcGMP reduced. Thus depleting intracellular Ca2+ stores attenuated the effect of SIN-1 and 8-BrcGMP, suggesting an involvement of functional Ca2+ stores.
我们研究了钾离子通道和细胞内钙离子库在大鼠离体回肠段中由一氧化氮供体3-吗啉代辛二亚胺（SIN-1）、8-溴环鸟苷（8-BrcGMP）、8-（4-氯苯硫基）环鸟苷（pCPT-cGMP）以及α,β-亚甲基三磷酸腺苷（α,β-methylene-ATP）诱导的舒张反应中的作用。对SIN-1和环鸟苷酸类似物的抑制反应不受钾离子阻滞剂蜂毒明肽、蝎毒素、iberiotoxin或格列本脲的影响，而α,β-亚甲基三磷酸腺苷诱导的舒张反应则被蜂毒明肽和四乙铵消除。一氧化氮供体SIN-1和环鸟苷酸类似物能够抑制由L型钙离子通道激活剂（BAY-K-8644）、卡巴胆碱（CCh）以及肌浆网钙离子-ATP酶阻滞剂环匹阿尼酸（CPA）诱导的收缩。然而，联合使用CPA和CCh时的抑制作用减弱，且SIN-1的剂量反应曲线右移。通过在无钙缓冲液中孵育以及用CCh或BAY-K-8644重复刺激来耗尽细胞内钙离子库。恢复细胞外钙离子后，SIN-1和pCPT-cGMP的抑制作用仅减弱，而在额外存在CPA的情况下，SIN-1的抑制作用被阻断，8-BrcGMP的作用减弱。因此，耗尽细胞内钙离子库会减弱SIN-1和8-BrcGMP的作用，提示功能性钙离子库参与其中。
