Modulation by neuropeptides of bradykinin-stimulated second messenger release in dorsal root ganglion neurons.
Modulation by neuropeptides of bradykinin-stimulated second messenger release in dorsal root ganglion neurons.
复制标题
神经肽对缓激肽刺激的背根神经节神经元第二信使释放的调节。
DOI：
10.1016/0006-8993(90)90967-g
复制
发表时间：
1990
期刊：
影响因子：
2.9
通讯作者：
Morell,P
中科院分区：
文献类型：
--
作者：
Gammon,CM;Lyons,SA;Morell,P
用[~H]花生四烯酸标记培养7~8天的胎鼠背根神经节神经元24 h，用10μM缓激肽(BK)刺激30只S，使其放射性甘油三酯和花生四烯酸水平增加近2倍。在没有受体刺激的情况下，用钙通道激动剂BAY K8644(10μM，含10 0 mM氯化钾)或钙离子载体离子载体离子霉素(2.5μM)也可得到类似的结果。如果加入电压敏感钙通道阻断剂3 mM的Co2+或2.5 mM的EDTA来抑制钙内流，则BK刺激的花生四烯酸和二甘油三酯的积累都被抑制。这些数据表明，在配体刺激下花生四烯酸(二甘油脂肪酶或磷脂酶A2的产物)和二甘油酯(磷脂酶C的产物)的积累都需要钙离子内流。这些反应可能涉及两类不同的通道，因为10μM硝苯地平或50μM维拉帕米(阻断部分电压敏感钙通道的药物)可抑制BK刺激的花生四烯酸蓄积，但不能抑制双甘酯的蓄积。这种功能区分似乎具有生理意义；硝苯地平和维拉帕米对BK刺激的花生四烯酸释放的抑制作用可通过减少背根神经节神经元钙通道电导的多肽来模拟。所用三种多肽分别为1μM神经肽Y、10μM生长抑素和10μM[N-MePhe3，d-Pro4]-吗啡肽。百日咳毒素可阻断神经肽Y的作用。我们得出结论，配体刺激的花生四烯酸释放可能被百日咳毒素敏感的G蛋白占据与钙通道亚群偶联的抑制性多肽位点所阻断。
Fetal rat dorsal root ganglion neurons (7–8 days in culture) were labeled with [3H]arachidonic acid for 24 h. Stimulation with 10 μM bradykinin (BK) for 30 s resulted in nearly 2-fold increases in levels of radioactive diglyceride and arachidonic acid. A similar result was obtained in the absence of receptor stimulation using the Ca2+channel agonist BAY K 8644 (10 μM, in the presence of 100 mM potassium chloride) or the Ca2+ionophore, ionomycin (2.5 μM). If Ca2+influx was inhibited by adding 3 mM Co2+, a blocker of voltage-sensitive calcium channels, or 2.5 mM EDTA, then BK-stimulated accumulation of both arachidonate and diglyceride was inhibited. These data suggest Ca2+influx is required for ligand-stimulated accumulation of both arachidonate (a product of diglyceride-lipase or phospholipase A2) and diglyceride (a product of phospholipase C). Two distinct populations of channels may be involved in these reactions since pretreatment with 10 μM nifedipine or 50 μM verapamil (agents which block a subset of voltage-sensitive Ca2+channels) inhibited BK-stimulated accumulation of arachidonic acid, but did not inhibit diglyceride accumulation. Such functional discrimination appears to have physiological importance; the inhibitory effect of nifedipine and verapamil on BK-stimulated arachidonate release was mimicked by pretreatment with peptides which decrease Ca2+channel conductance in dorsal root ganglion neurons. The three peptides used were 1 μM neuropeptide Y, 10 μM somatostatin, and 10 μM[N-MePhe3,d-Pro4]-morphiceptin. The effect of neuropeptide Y was blocked by pretreatment with pertussis toxin. We conclude that ligand-stimulated arachidonic acid release may be blocked by occupation of inhibitory peptide sites coupled to a subset of calcium channels by a pertussis toxin sensitive G-protein.