Influence of nicotine and cotinine on retinal phospholipase A2 and its significance to macular function

被引:27
作者
Sastry, BVR [1 ]
Hemontolor, ME [1 ]
机构
[1] Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Nashville, TN 37232 USA
关键词
D O I
10.1089/jop.1998.14.447
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
The macula is a constituent of the sensory retina that is necessary for sharp contrast and color vision. A significant relationship has been found between tobacco smoking and age-related macular degeneration. Opsin, rhodopsin and phospholipase A(2) (PLA(2)) are located in excitable membranes of retina which are enriched with polyunsaturated fatty acids (PUFA). A question may arise as to whether nicotine and its major metabolite cotinine influence PLA(2) so that arachidonic acid (AA) and proinflammatory prostaglandins (PG) are produced in the retina. Therefore, the effects of nicotine and cotinine on the retinal. PLA(2) were studied. PLA(2) activity of rat retinal sonicates was assayed using 1-palmitoyl-2[1-C-14]arachidonyl-Phosphatidylethanolamine (PE, 2.2 nmol) as a substrate in Tris buffer (10 mM, pH 7.4) at 37 degrees C with and without nicotine or cotinine in the assay medium. These studies gave the following results: (I) Rat retinal PLA(2) activity was 4.2 +/- 0.8 pmol PE hydrolyzed/100 ng protein/hr. (2) Nicotine in low concentrations (1-150 nM) activated PLA(2) (EC50 5nM). (3) Cotinine also activated PLA(2) (EC50 300 nM). (4) Only high concentrations of nicotine (> 1.0 mu M) and cotinine (> 25 mu M) exhibit inhibition of PLA(2). (5) All three known PLA(2) inhibitors, mepacrine, 4-bromophenacyl bromide and bromoacetylcholine bromide (IC50: 0.5mM, 88 mu M, 30mM, respectively) inhibited retinal PLA(2) activity. These observations suggest that polyunsaturated fatty acids are cleaved, and arachidonic acid, the precursor for prostaglandins and related pro-inflammatory mediators, is liberated by nicotine and cotinine. Oxidative stress (reduced levels of antioxidants), vascular insufficiency, as well as activation of PLA(2) by nicotine and cotinine may contribute for retinal degeneration in smokers during aging.
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页码:447 / 458
页数:12
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