Scavone C, Glezer I, Demarchi Munhoz C, de Sena Bernardes C, Pekelmann Markus R
Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, Av. Lineu Prestes 1524, 05508-900, São Paulo, Brazil.
Eur J Pharmacol. 2000 Jan 24;388(1):1-7. doi: 10.1016/s0014-2999(99)00850-x.
Age-related changes in the modulatory action of nitric oxide (NO) on cyclic GMP levels and Na(+),K(+)-ATPase activity in the proximal rat trachea were investigated using sodium nitroprusside, 8-bromo-cyclic GMP and okadaic acid. At 24 months, both control activities of Na(+), K(+)-ATPase and Mg(2+)-ATPase were decreased when compared to the segments from 4- and 12-month-old animals. However, cyclic GMP levels were similar among the three ages. Sodium nitroprusside (100 microM) induced stimulation of Na(+),K(+)-ATPase activity in segments from both 4- and 12-month-old animals, but not 24-month-old animals. The effect was specific for Na(+),K(+)-ATPase since Mg(2+)-ATPase activity was unaffected. Sodium nitroprusside induced an increase in nitrates/nitrites and cyclic GMP levels in proximal segments at 4, 12 and 24 months. The 8-bromo-cyclic GMP (100 microM) induced a similar specific stimulation of Na(+),K(+)-ATPase activity in segments from 4- and 12- but not 24-month-old animals. Okadaic acid (1 microM), a phosphatase-1 inhibitor, increased proximal Na(+), K(+)-ATPase but not Mg(2+)-ATPase activity in tissues from 4-, 12- and 24-month-old animals. Our results suggest that aging affects cyclic GMP pathway in proximal rat trachea by an action at the level of the cyclic GMP-dependent protein kinase.
利用硝普钠、8-溴环鸟苷酸和冈田酸，研究了一氧化氮（NO）对大鼠近端气管中环鸟苷酸水平及钠钾ATP酶活性的调节作用随年龄的变化。与4月龄和12月龄动物的气管节段相比，24月龄动物的钠钾ATP酶和镁ATP酶的对照活性均降低。然而，三个年龄段的环鸟苷酸水平相似。硝普钠（100微摩尔）可刺激4月龄和12月龄动物气管节段的钠钾ATP酶活性，但对24月龄动物无效。该作用对钠钾ATP酶具有特异性，因为镁ATP酶活性未受影响。硝普钠可使4月龄、12月龄和24月龄动物近端气管节段的硝酸盐/亚硝酸盐及环鸟苷酸水平升高。8-溴环鸟苷酸（100微摩尔）对4月龄和12月龄动物气管节段的钠钾ATP酶活性有类似的特异性刺激作用，但对24月龄动物无效。磷酸酶-1抑制剂冈田酸（1微摩尔）可增加4月龄、12月龄和24月龄动物组织近端的钠钾ATP酶活性，但不影响镁ATP酶活性。我们的结果表明，衰老通过作用于环鸟苷酸依赖性蛋白激酶水平影响大鼠近端气管的环鸟苷酸途径。
