Watanabe Shun, Matsumoto Takayuki, Taguchi Kumiko, Kobayashi Tsuneo
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.
Can J Physiol Pharmacol. 2017 Apr;95(4):459-462. doi: 10.1139/cjpp-2016-0372. Epub 2017 Jan 24.
We studied the relationship between 3-phosphoinositide-dependent protein kinase 1 (PDK1) and contractions induced by serotonin, phenylephrine, and thromboxane A mimetic (U46619) in the presence of nitric oxide synthase inhibitor in the carotid arteries of Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetic model, in the chronic stage of disease. Serotonin-induced contraction was greater in the GK rats than in the control Wistar rats. A specific PDK1 inhibitor (GSK2334470) decreased the serotonin-induced contraction in the GK rats but not in the Wistar rats, and the difference in such contraction was abolished with this treatment. In GK rats, phenylephrine-induced contraction exhibited a leftward shift and U46619-induced contraction was greater still. Phenylephrine- and U46619-induced contractions were reduced by GSK2334470 in both groups. These results suggest, for the first time, that the contribution of PDK1 is different among 3 vasoconstrictors and that PDK1 contributed to increased serotonin-induced contraction in the carotid arteries of GK rats.
我们研究了在疾病慢性期的自发性2型糖尿病模型——Goto-Kakizaki（GK）大鼠的颈动脉中，在一氧化氮合酶抑制剂存在的情况下，3-磷酸肌醇依赖性蛋白激酶1（PDK1）与血清素、去氧肾上腺素和血栓素A类似物（U46619）诱导的收缩之间的关系。血清素诱导的收缩在GK大鼠中比在对照Wistar大鼠中更大。一种特异性PDK1抑制剂（GSK2334470）可降低GK大鼠中血清素诱导的收缩，但对Wistar大鼠无效，并且这种收缩差异通过该处理被消除。在GK大鼠中，去氧肾上腺素诱导的收缩表现出向左移位，而U46619诱导的收缩更大。两组中，GSK2334470均可降低去氧肾上腺素和U46619诱导的收缩。这些结果首次表明，PDK1在三种血管收缩剂中的作用不同，且PDK1促成GK大鼠颈动脉中血清素诱导的收缩增加。
