Catalán R E, Martínez A M, Aragonés M D, Hernández F, Liras A, Miguel B G
Departamento de Biología Molecular, Universidad Autónoma de Madrid, Spain.
Neurochem Res. 1995 Oct;20(10):1147-53. doi: 10.1007/BF00995377.
We have suggested that substance P, in cerebral cortex, causes a phosphatidylinositol (PI) breakdown by a dual mechanism suggesting the involvement of either phospholipase A2 or phospholipase C. We have presently characterized further these effects. Substance P (65 pM) provoked an increase in lysoPI concomitant with a decrease in PI level. This finding confirms the involvement of phospholipase A2 activation. To study the involvement of phospholipase C in the action of higher doses (0.65 microM) of the peptide, we used pulse-chase experiments (where phospholipid depletion was monitored) and short-term 32P-labeled slices (where phospholipid synthesis was studied). Substance P evoked an acceleration of both hydrolysis and resynthesis of PI as early as 15 s. A prolonged exposure (30 min) resulted in stimulation of PI hydrolysis without subsequent resynthesis. The peptide did not cause any effect on inositol 1,4-bisphosphate and inositol 1,4,5-trisphosphate. These alterations in PI metabolism take place simultaneously with a generation of diacylglycerol which showed two maxima at both indicated times.
我们曾提出，在大脑皮层中，P物质通过一种双重机制导致磷脂酰肌醇（PI）分解，这表明磷脂酶A2或磷脂酶C参与其中。我们目前进一步对这些效应进行了表征。P物质（65皮摩尔）引起溶血磷脂酰肌醇增加，同时PI水平降低。这一发现证实了磷脂酶A2激活的参与。为了研究磷脂酶C在高剂量（0.65微摩尔）该肽作用中的参与情况，我们进行了脉冲追踪实验（监测磷脂消耗）和短期32P标记切片实验（研究磷脂合成）。P物质早在15秒时就引起PI水解和再合成的加速。长时间暴露（30分钟）导致PI水解受到刺激，但随后没有再合成。该肽对肌醇1,4-二磷酸和肌醇1,4,5-三磷酸没有任何影响。PI代谢的这些改变与二酰基甘油的生成同时发生，二酰基甘油在两个指定时间均出现两个峰值。
