Department of Physiology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung City, Taiwan, China.
J Neurochem. 2010 Aug;114(4):1217-30. doi: 10.1111/j.1471-4159.2010.06843.x. Epub 2010 Jun 1.
Hypothalamic neuropeptide Y (NPY) has been reported to involve in regulating behavioral response of phenylpropanolamine (PPA), a sympathomimetic agent. This study explored if protein kinase C (PKC)-delta signaling participated in this regulation. Moreover, possible roles of anti-free radical enzyme catalase (CAT) and nitrogen oxide synthase (NOS) were also examined. Rats were treated daily with PPA for 4 days. Changes in food intake and hypothalamic NPY, PKCdelta, CAT, and NOS contents were assessed and compared. Results showed that PKCdelta and CAT increased during PPA treatment, which were concomitant with decreases in NPY content and food intake, while the change of NOS was expressed differently. Moreover, PKCdelta knockdown could modify PPA anorexia as well as NPY and CAT expression, while NOS expression remained unchanged. Furthermore, pre-treatment with NOS inhibitor could modify both PPA anorexia and NPY content. It is suggested that PKCdelta participates in the anorectic response of PPA via the modulation of NPY and CAT, while NOS contribute to this modulation via a different mechanism during PPA treatment. Results provide molecular mechanism of NPY-mediated PPA anorexia and may aid the therapeutic research of PPA and other anti-obesity drugs.
下丘脑神经肽 Y (NPY) 已被报道参与调节苯丙醇胺 (PPA) 的行为反应，苯丙醇胺是一种拟交感胺。本研究探讨了蛋白激酶 C (PKC)-δ 信号是否参与这种调节。此外，还研究了抗氧化酶过氧化氢酶 (CAT) 和一氧化氮合酶 (NOS) 的可能作用。大鼠每天用 PPA 处理 4 天。评估并比较了食物摄入量和下丘脑 NPY、PKCδ、CAT 和 NOS 含量的变化。结果表明，PKCδ和 CAT 在 PPA 处理期间增加，同时 NPY 含量和食物摄入量减少，而 NOS 的变化则表现不同。此外，PKCδ 敲低可以改变 PPA 引起的厌食以及 NPY 和 CAT 的表达，而 NOS 的表达保持不变。此外，NOS 抑制剂的预处理可以改变 PPA 引起的厌食和 NPY 含量。结果表明，PKCδ 通过调节 NPY 和 CAT 参与 PPA 的厌食反应，而 NOS 通过不同的机制在 PPA 处理过程中对这种调节做出贡献。研究结果提供了 NPY 介导的 PPA 厌食的分子机制，并可能有助于 PPA 和其他减肥药的治疗研究。
