DeGeorge J J, Morell P, McCarthy K D, Lapetina E G
J Biol Chem. 1986 Mar 5;261(7):3428-33.
Glioma C62B cells were incubated for 18 h with [1-14C]arachidonic acid. Most (80%) of the added [1-14C] arachidonic acid was taken into the intracellular pool; less than 1% of the intracellular [1-14C]arachidonic acid remained unesterified; the rest was present in glycerophospholipids. Acetylcholine stimulation of the prelabeled cells resulted in the rapid accumulation of free [1-14C]arachidonic acid, presumably liberated by hydrolysis from phospholipids. Labeled unesterified [1-14C]arachidonic acid peaked by 90 s and returned to basal levels by 5 min. Paralleling the transient increase of unesterified [1-14C]arachidonic acid were increases in level of radioactivity in an unidentified lipoxygenase metabolite of arachidonic acid and of radioactive phosphatidic acid. The release of arachidonic acid induced by acetylcholine or carbachol was blocked by muscarinic but not nicotinic receptor antagonists; adrenergic or histaminergic receptor agonists were ineffective at stimulating arachidonic acid liberation. In contrast to the transient effects of stimulation with cholinergic agonists, stimulation with the divalent cation ionophore A23187 resulted in a linear increase in the accumulation of liberated arachidonic acid for at least 1 h. Furthermore, the pattern of metabolites synthesized from arachidonic acid in response to ionophore stimulation was more complex than that observed following cholinergic stimulation and included also several metabolites derived from cyclooxygenase activity. We conclude that muscarinic receptor agonists rapidly induce specific changes in arachidonic acid and phosphatidic acid metabolism in a glioma cell line and suggest that similar responses may occur in glial cells and play a physiologically significant role in neural metabolism.
将胶质瘤C62B细胞与[1-14C]花生四烯酸一起孵育18小时。添加的[1-14C]花生四烯酸大部分（80%）进入细胞内池；细胞内[1-14C]花生四烯酸中未酯化的不到1%；其余存在于甘油磷脂中。对预先标记的细胞进行乙酰胆碱刺激导致游离[1-14C]花生四烯酸迅速积累，推测是通过磷脂水解释放出来的。标记的未酯化[1-14C]花生四烯酸在90秒时达到峰值，并在5分钟时恢复到基础水平。与未酯化[1-14C]花生四烯酸的短暂增加相平行的是花生四烯酸的一种未鉴定的脂氧合酶代谢产物和放射性磷脂酸的放射性水平增加。乙酰胆碱或卡巴胆碱诱导的花生四烯酸释放被毒蕈碱受体拮抗剂阻断，而不是烟碱受体拮抗剂；肾上腺素能或组胺能受体激动剂在刺激花生四烯酸释放方面无效。与胆碱能激动剂刺激的短暂效应相反，用二价阳离子载体A23187刺激导致释放的花生四烯酸积累呈线性增加，至少持续1小时。此外，离子载体刺激后由花生四烯酸合成的代谢产物模式比胆碱能刺激后观察到的更复杂，还包括几种来自环氧化酶活性的代谢产物。我们得出结论，毒蕈碱受体激动剂在胶质瘤细胞系中迅速诱导花生四烯酸和磷脂酸代谢的特定变化，并表明类似的反应可能在神经胶质细胞中发生，并在神经代谢中发挥生理上重要的作用。
