Caspers M L, Kwaiser T M, Dow M J, Fu M J, Grammas P
Department of Chemistry, University of Detroit Mercy, MI 48219.
Mol Chem Neuropathol. 1993 May-Jun;19(1-2):65-81. doi: 10.1007/BF03160169.
The Na+,K(+)-ATPase is an important enzyme in determining the ionic milieu of the cerebromicrovasculature and neurons. The effect of hypertension or aging on this enzyme, as well as its susceptibility to regulation by fatty acids or aluminum, is the focus of this study. A significant increase (34%) in the apparent affinity constant (KD) but no change in the maximum binding capacity (Bmax) for [3H]ouabain binding to the cerebromicrovascular Na+,K(+)-ATPase occurs after induction of acute hypertension. In addition, long chain unsaturated fatty acids stimulate the binding of [3H]ouabain to the enzyme in microvessels from normotensive and hypertensive rats. The synaptosomal Na+,K(+)-ATPase is sensitive to aluminum. AlCl3 (1-100 microM) inhibits the K(+)-dependent-p-nitrophenylphosphatase (K(+)-NPPase) activity of the Na+,K(+)-ATPase in a dose-dependent manner. AlCl3 (100 microM) decreases the Vmax by 14% but does not alter the KM, suggestive of non-competitive inhibition. The enzyme from aged brain displays a greater Vmax, but shows the same susceptibility to AlCl3 as the enzyme from younger brain. In summary, disruption of the Na+,K(+)-ATPase may underlie, at least in part, abnormalities of nerve and vascular cell function in disorders where elevated concentrations of fatty acids or metal ions are involved.
钠钾ATP酶是决定脑微血管和神经元离子环境的一种重要酶。高血压或衰老对该酶的影响，以及其对脂肪酸或铝调节的敏感性，是本研究的重点。急性高血压诱导后，[3H]哇巴因与脑微血管钠钾ATP酶结合的表观亲和常数（KD）显著增加（34%），但最大结合容量（Bmax）无变化。此外，长链不饱和脂肪酸刺激正常血压和高血压大鼠微血管中[3H]哇巴因与该酶的结合。突触体钠钾ATP酶对铝敏感。AlCl3（1-100 microM）以剂量依赖方式抑制钠钾ATP酶的钾依赖性对硝基苯磷酸酶（K(+)-NPPase）活性。AlCl3（100 microM）使Vmax降低14%，但不改变KM，提示为非竞争性抑制。老年脑的该酶显示出更高的Vmax，但对AlCl3的敏感性与年轻脑的酶相同。总之，至少在一定程度上，脂肪酸或金属离子浓度升高的疾病中神经和血管细胞功能异常可能是由钠钾ATP酶的破坏所致。
