Modulation of Na, K-ATPase activity by prostaglandin E1 and [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin.
Modulation of Na, K-ATPase activity by prostaglandin E1 and [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin.
复制标题
前列腺素 E1 和 [D-Ala2,N-Me-Phe4,Gly5-ol]-脑啡肽调节 Na、K-ATP 酶活性。
DOI：
10.1016/j.lfs.2005.07.005
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Specht,SusanC
中科院分区：
文献类型：
--
作者：
Woolcock,Karen;Specht,SusanC
腺苷酸环化酶被前列腺素E激活并被μ阿片类药物抑制。由于cAMP相关事件影响许多系统中Na泵及其生化相关Na，K-ATP酶的活性，我们验证了前列腺素E1和μ-阿片激动剂[d-Ala 2，N-Me-Phe 4，Gly 5-ol]-脑啡肽（DAMGO）对Na，K-ATP酶活性具有相反作用的假设。使用丙氨甲菌素透化的SH-SY 5 Y人神经母细胞瘤细胞进行研究。前列腺素E1（1 μM）可短暂抑制Na，K-ATP酶活性10-15分钟。蛋白激酶A的直接激活剂8-Br-cAMP（150和500 μM）也可抑制Na，K-ATP酶活性，但抑制速度更快，持续时间更短。DAMGO（1 μM）和RP-腺苷3′，5 ′-环硫代磷酸（500 μM）（一种蛋白激酶A抑制剂）均可逆转前列腺素E1的抑制作用。单独的DAMGO（1 μM）刺激Na，K-ATP酶活性高达对照活性的近3倍。DAMGO的刺激作用可被钙调神经磷酸酶抑制剂环孢菌素A（2 μM）阻断，并且依赖于Ca 2+通过硝苯地平敏感性Ca 2+通道进入。在1 mM EGTA存在下，DAMGO抑制Na，K-ATP酶活性。DAMGO诱导的抑制作用可被1，4，5-三磷酸肌醇受体拮抗剂xestospongin C（1 μM）阻断。Na，K-ATP酶通过其维持膜电位和跨膜离子梯度的作用来调节神经元的兴奋性。前列腺素E1和阿片类药物对Na，K-ATP酶活性的不同影响可能与它们在痛觉过敏中的作用有关。
Adenylyl cyclase is activated by prostaglandin E and inhibited by mu-opioids. Since cAMP-related events influence the activity of the Na Pump and its biochemical correlate Na,K-ATPase in many systems, we tested the hypothesis that prostaglandin E1and [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO), a mu-opioid agonist, have opposing actions on Na,K-ATPase activity. Studies were conducted with alamethicin-permeabilized SH-SY5Y human neuroblastoma cells. Prostaglandin E1(1 μM) transiently inhibited Na,K-ATPase activity for 10–15 min. A direct activator of protein kinase A, 8-Br-cAMP (150 and 500 μM), also inhibited, but more rapidly and for a shorter duration. Both DAMGO (1 μM) and Rp-adenosine 3′,5′-cyclic monophosphorothioate (500 μM), a protein kinase A-inhibitor, reversed the inhibitory effect of prostaglandin E1. DAMGO alone (1 μM) stimulated Na,K-ATPase activity up to nearly three-fold control activity. The stimulatory action of DAMGO was blocked by cyclosporine A (2 μM), an inhibitor of calcineurin, and was dependent on Ca2+entry through nifedipine-sensitive Ca2+channels. In the presence of 1 mM EGTA, DAMGO inhibited Na,K-ATPase activity. DAMGO-induced inhibition was blocked by the inositol 1,4,5-trisphosphate receptor antagonist xestospongin C (1 μM). Na,K-ATPase is poised to modulate neuronal excitability through its roles in maintaining the membrane potential and transmembrane ion gradients. The differential effects of prostaglandin E1and opioids on Na,K-ATPase activity may be related to their actions in hyperalgesia.