Marczin N, Papapetropoulos A, Jilling T, Catravas J D
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912-2300.
Br J Pharmacol. 1993 Jul;109(3):603-5. doi: 10.1111/j.1476-5381.1993.tb13613.x.
We investigated the role of microtubules in the induction of nitric oxide synthase in cultured vascular smooth muscle cells. We found that like interleukin-1 alpha, lipopolysaccharide elicited a time and concentration-dependent accumulation of cyclic GMP via induction of nitric oxide synthase. Nocodazole and colchicine, two chemically distinct microtubule depolymerizing agents, completely prevented lipopolysaccharide- and interleukin-induced (and nitric oxide-mediated) cyclic GMP generation. In contrast to lipopolysaccharide and interleukin-1 alpha, cyclic GMP accumulation in response to sodium nitroprusside, an exogenous nitrovasodilator, was not altered by either nocodazole or colchicine. Our findings demonstrate that microtubule depolymerizing agents inhibit nitric oxide synthase induction and suggest a prominent role for microtubules in mediating the activation of the inducible nitric oxide pathway in smooth muscle cells.
我们研究了微管在培养的血管平滑肌细胞中一氧化氮合酶诱导过程中的作用。我们发现，与白细胞介素-1α一样，脂多糖通过诱导一氧化氮合酶引发环鸟苷酸的时间和浓度依赖性积累。诺考达唑和秋水仙碱，两种化学性质不同的微管解聚剂，完全阻止了脂多糖和白细胞介素诱导的（以及一氧化氮介导的）环鸟苷酸生成。与脂多糖和白细胞介素-1α不同，外源性硝基血管扩张剂硝普钠引起的环鸟苷酸积累不受诺考达唑或秋水仙碱的影响。我们的研究结果表明，微管解聚剂抑制一氧化氮合酶的诱导，并提示微管在介导平滑肌细胞中诱导型一氧化氮途径的激活中起重要作用。
