Grynberg A, Fournier A, Sergiel J P, Athias P
I.N.R.A. Unité de Nutrition Lipidique, Dijon, France.
J Mol Cell Cardiol. 1995 Nov;27(11):2507-20. doi: 10.1006/jmcc.1995.0238.
The specific effect of docosahexaenoic (DHA; C22:6 n-3), as compared to eicosapentaenoic acid (EPA; C20:5 n-3), on adrenoceptor function was investigated in cultured rat myocardial cells. The cardiomyocytes were grown for 24 h in a conventional seric medium, and then incubated for 96 h in a medium enriched with either DHA or EPA. After this treatment, the phospholipids of the DHA-treated cells contained approximately 20% of the total fatty acids as C22:6 n-3, and those of EPA-treated cells displayed a high content in C20:5 n-3 and its elongation product C22:5 n-3 (30% of total fatty acids). Additionally, the n-3/n-6 polyunsaturated fatty acid ratio was the same in the two groups of cells. These modifications were roughly similar in all the phospholipid classes. The contractions were monitored photometrically and no significant difference in basal frequency and contraction parameters could be detected. The stimulation of the beta-adrenergic receptors (isoproterenol 10(-7) M) resulted in a positive chronotropic effect, which was significantly higher in the DHA-rich cells. Conversely, the higher DHA content in the phospholipids appeared to induce a decrease in the affinity of the beta-receptors for the ligand (dihydroalprenolol) without alteration of the number of beta-receptor binding sites and provoked a significant decrease in isoproterenol-stimulated cAMP production (-19%). To investigate further these controversial data, the cardiomyocytes were treated with dibutyryl-cAMP, which elicited a positive chronotropic response significantly higher in the DHA-rich cells. The alpha-adrenergic stimulation by phenylephrine (3 x 10(-6) M) increased the spontaneous rate, but in a similar manner in the DHA- and EPA-enriched cells. Similarly, neither the alpha-adrenergic receptor binding characteristics nor the production of phosphoinositides was modulated by the membrane DNA content, although the phosphatidylinositol PUFAs were significantly altered. In conclusion, increasing the DHA content in membrane phospholipids did not affect the alpha-adrenergic system, but exerted a specific positive influence on the beta-adrenergic transduction mechanism, essentially through an increase of cAMP efficiency.
在培养的大鼠心肌细胞中，研究了二十二碳六烯酸（DHA；C22:6 n-3）与二十碳五烯酸（EPA；C20:5 n-3）相比，对肾上腺素能受体功能的特定影响。心肌细胞在常规含血清培养基中培养24小时，然后在富含DHA或EPA的培养基中孵育96小时。经过这种处理后，用DHA处理的细胞的磷脂中约20%的总脂肪酸为C22:6 n-3，而用EPA处理的细胞的磷脂中C20:5 n-3及其延长产物C22:5 n-3含量较高（占总脂肪酸的30%）。此外，两组细胞中n-3/n-6多不饱和脂肪酸的比例相同。所有磷脂类中的这些变化大致相似。通过光度法监测收缩情况，未检测到基础频率和收缩参数有显著差异。β-肾上腺素能受体的刺激（异丙肾上腺素10(-7) M）导致正性变时效应，在富含DHA的细胞中显著更高。相反，磷脂中较高的DHA含量似乎会导致β-受体对配体（二氢阿普洛尔）的亲和力降低，而β-受体结合位点的数量没有改变，并导致异丙肾上腺素刺激的cAMP产生显著降低（-19%）。为了进一步研究这些有争议的数据，用二丁酰-cAMP处理心肌细胞，其在富含DHA的细胞中引发的正性变时反应显著更高。苯肾上腺素（3×10(-6) M）对α-肾上腺素能的刺激增加了自发频率，但在富含DHA和EPA的细胞中方式相似。同样，尽管磷脂酰肌醇多不饱和脂肪酸发生了显著变化，但α-肾上腺素能受体结合特性和磷酸肌醇的产生均未受到膜中DHA含量调节。总之，增加膜磷脂中的DHA含量不会影响α-肾上腺素能系统，但对β-肾上腺素能转导机制有特定的积极影响，主要是通过提高cAMP效率实现的。
