Lindmar R, Löffelholz K, Sandmann J
Department of Pharmacology, University of Mainz, Federal Republic of Germany.
Biochem Pharmacol. 1988 Dec 15;37(24):4689-95. doi: 10.1016/0006-2952(88)90339-5.
In the heart, choline phospholipids were by far the largest fraction (about 50%) of phospholipids, much larger than that of inositol phospholipids (less than 6%) and phosphatidic acid (0.3%). The choline phospholipids (11 mumol/g) maintained a constant efflux of choline of about 1.5 nmol g-1 min-1 into the perfusate. Carbachol (10 microM) rapidly enhanced the choline efflux by a muscarinic mechanism, that was independent of mepacrine, an inhibitor of phospholipase A2, as well as of extracellular Ca2+; the maximum acceleration was reached within 2 min. In contrast, the accumulation of inositol phosphates by carbachol was blocked in the presence of a Ca2+-free perfusion medium. Similar to the carbachol-evoked choline efflux, the increase in tissue content of phosphatidic acid by carbachol was unaffected by infusion of a Ca2+-free, EGTA-containing solution. Sodium oleate (20 microM), an activator of phospholipase D, imitated the effects of carbachol on choline and phosphatidic acid, whereas NaF (5 mM), which has been reported to inhibit phospholipase D, blocked carbachol-evoked efflux of choline. In conclusion, muscarinic receptor stimulation enhanced the hydrolysis of choline phospholipids presumably via activation of phospholipase D. The immediate formation of choline, phosphatidic acid and presumably diacylglycerol is discussed including its possible physiological importance.
在心脏中，胆碱磷脂是磷脂中占比最大的部分（约50%），远大于肌醇磷脂（不到6%）和磷脂酸（0.3%）。胆碱磷脂（11 μmol/g）向灌注液中持续稳定地流出胆碱，流出速率约为1.5 nmol g-1 min-1。卡巴胆碱（10 μM）通过毒蕈碱机制迅速增强胆碱流出，该机制独立于磷脂酶A2抑制剂米帕林以及细胞外Ca2+；在2分钟内达到最大加速。相反，在无Ca2+灌注液存在的情况下，卡巴胆碱引起的肌醇磷酸积累被阻断。与卡巴胆碱引起的胆碱流出相似，卡巴胆碱使磷脂酸组织含量增加不受无Ca2+、含乙二醇双四乙酸（EGTA）溶液灌注的影响。油酸纳（20 μM）作为磷脂酶D的激活剂，模拟了卡巴胆碱对胆碱和磷脂酸的作用，而据报道能抑制磷脂酶D的氟化钠（5 mM）则阻断了卡巴胆碱引起的胆碱流出。总之，毒蕈碱受体刺激可能通过激活磷脂酶D增强胆碱磷脂的水解。本文讨论了胆碱、磷脂酸以及可能的二酰基甘油的即时形成及其可能的生理重要性。
