Missiaen L, Kanmura Y, Wuytack F, Raeymaekers L, Declerck I, Droogmans G, Casteels R
Physiological Laboratory, Katholieke Universiteit Leuven, Belgium.
Pflugers Arch. 1989 Aug;414(4):423-9. doi: 10.1007/BF00585052.
AlF-4, known to be a potent modulator of G-proteins, also inhibits purified "P"-type cation-transport ATPases (Missiaen et al. 1988). The aim of the present work is to find out whether AlF-4 also inhibits these ATPases in intact cells. We therefore have studied the effect of AlF-4 on the force development and on 45Ca2+ -fluxes of muscle strips from rat myometrium and rabbit ear artery. 1 mM-NaF plus 10 microM-AlCl3 induces in both tissues a tonic contraction that is completely blocked by 0.5 mM-deferoxamine. The contractile response in myometrium exceeds that of the ear artery. These contractions are independent of an activation of G-proteins but their amplitude depends on [Ca2+]o. Application of AlF-4 during the loading of the endoplasmic reticulum of myometrium with Ca2+ dramatically reduces the amount of stored Ca2+ as estimated from its release induced by 1 mM-carbachol during incubation in Ca-free solution. This effect could be due to a predominant inhibitory effect of AlF-4 on the (Ca2+ + Mg2+)-ATPase of the endoplasmic reticulum. Such effect could not be established in rabbit ear artery. The increase of the fractional loss of 45Ca2+ induced by 10 microM-norepinephrine in rabbit ear artery is not inhibited by AlF-4. It is concluded that the inhibition of the endoplasmic-reticulum (Ca2+ + Mg2+)-ATPase in intact myometrial cells warns us against explaining all effects of AlF-4 on intact cells only by an activation of G-proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
已知AlF-4是G蛋白的强效调节剂,它也能抑制纯化的“P”型阳离子转运ATP酶(米西亚恩等人,1988年)。本研究的目的是确定AlF-4在完整细胞中是否也能抑制这些ATP酶。因此,我们研究了AlF-4对大鼠子宫肌层和兔耳动脉肌条的力产生以及45Ca2+通量的影响。1 mM氟化钠加10 microM氯化铝在两种组织中均诱导出强直性收缩,该收缩被0.5 mM去铁胺完全阻断。子宫肌层的收缩反应超过兔耳动脉。这些收缩与G蛋白的激活无关,但其幅度取决于细胞外钙离子浓度。在子宫肌层内质网加载钙离子的过程中应用AlF-4,显著降低了储存的钙离子量,这是根据在无钙溶液中孵育时1 mM卡巴胆碱诱导的钙离子释放量估算得出的。这种效应可能是由于AlF-4对内质网(Ca2+ + Mg2+)-ATP酶的主要抑制作用。在兔耳动脉中未发现这种效应。10 microM去甲肾上腺素诱导的兔耳动脉中45Ca2+分数损失的增加未被AlF-4抑制。得出的结论是,完整子宫肌层细胞内质网(Ca2+ + Mg2+)-ATP酶的抑制提醒我们,不能仅通过G蛋白的激活来解释AlF-4对完整细胞的所有作用。(摘要截短至250字)