Murphy M G, Byczko Z
Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada.
Adv Exp Med Biol. 1992;318:91-102. doi: 10.1007/978-1-4615-3426-6_8.
Studies have demonstrated that augmenting the omega 6 polyunsaturated-fatty-acid (PUFA) content of N1E-115 neuroblastoma cells by media supplementation with linoleic acid results in greater than or equal to 2-fold increases in basal levels of intracellular cyclic AMP (cAMP). Data suggested some involvement of increased production of adenosine from endogenous metabolites; however, increases in adenosine were not related to increased activity of 5'-nucleotidase or decreased uptake of extracellular adenosine. PUFA-dependent elevations in basal cAMP were evident within 1 min of exposure to a phosphodiesterase inhibitor; this phenomenon did not appear to be due to PUFA-dependent changes in Ca2+ uptake or to increases in sensitivity of adenylate cyclase to Ca2+. Forskolin-stimulated cAMP formation was 3-fold higher in PUFA-enriched cells than in control cells, which suggested a direct effect on the functioning of the catalytic unit. Linoleic acid supplementation resulted in a 2-fold increase in the maximum amounts of cAMP produced in response to the stable adenosine analogue, 5'-N'ethylcarboxy-amidoadenosine (NECA). The altered stimulatory response did not involve eicosanoid formation, but may have been related to an increase in the number of stimulatory adenosine receptors, as judged by binding of [3H]NECA. These studies indicate that membrane PUFA modulate adenosine-related functions in neuroblastoma cells, and suggest that a complex series of mechanisms is involved in this regulation.
研究表明，通过在培养基中添加亚油酸来增加N1E - 115神经母细胞瘤细胞中ω-6多不饱和脂肪酸（PUFA）的含量，会使细胞内环状AMP（cAMP）的基础水平提高2倍或更多。数据表明内源性代谢产物产生的腺苷增加可能起到了一定作用；然而，腺苷的增加与5'-核苷酸酶活性的增加或细胞外腺苷摄取的减少无关。在暴露于磷酸二酯酶抑制剂的1分钟内，PUFA依赖性的基础cAMP升高就很明显；这种现象似乎不是由于PUFA依赖性的Ca2+摄取变化或腺苷酸环化酶对Ca2+敏感性的增加所致。在富含PUFA的细胞中，福斯高林刺激的cAMP形成比对照细胞高3倍，这表明对催化单元的功能有直接影响。添加亚油酸使对稳定腺苷类似物5'-N'-乙基羧基酰胺腺苷（NECA）产生反应时产生的cAMP最大量增加了2倍。刺激反应的改变并不涉及类花生酸的形成，但可能与刺激型腺苷受体数量的增加有关，这是通过[3H]NECA的结合判断的。这些研究表明，膜PUFA调节神经母细胞瘤细胞中与腺苷相关的功能，并表明这一调节过程涉及一系列复杂的机制。
