Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing Institute of Cardiology, Chongqing Cardiovascular Clinical Research Center, Chongqing 400042, P.R. China.
Mol Med Rep. 2017 Oct;16(4):5606-5610. doi: 10.3892/mmr.2017.7271. Epub 2017 Aug 17.
Abnormal migration of vascular smooth muscle cells (VSMCs) serves an important role in hypertension, atherosclerosis and restenosis following angioplasty, which is regulated numerous hormonal and humoral factors, including neuropeptide Y (NPY) and dopamine. Dopamine and NPY are both sympathetic neurotransmitters, and a previous study reported that NPY increased VSMC proliferation, while dopamine receptor inhibited it. Therefore, the authors wondered whether or not there is an inhibitory effect of dopamine receptor on NPY‑mediated VSMC migration. The present study demonstrated that stimulation with NPY dose‑dependence (10‑10‑10‑7M, 24 h) increased VSMC migration, the stimulatory effect of NPY was via the Y1 receptor. This is because, in the presence of the Y1 receptor antagonist, BIBP3226 (10‑7 M), the stimulatory effect of NPY on VSMC migration was blocked. Activation of the D3 receptor by PD128907 dose‑dependence (10‑11‑10‑8 M) reduced the stimulatory effect of NPY on VSMC migration. The effect of PD128907 was via the D3 receptor, because the inhibitory effect of PD128907 on NPY‑mediated migration was blocked by the D3 receptor antagonist, U99194. The authors' further study suggested that the inhibitory effect of the D3 receptor was via the PKA signaling pathway, in the presence of the PKA inhibitor, 14‑22 (10‑6 M), the inhibitory effect of PD128907 on VSMC migration was blocked. Moreover, the inhibitory effect of PD128907 was imitated by PKA activator, Sp‑cAMP [S], in the presence of Sp‑cAMP [S], the NPY‑mediated stimulatory effect on VSMC migration was abolished. The present study indicated that activation of the D3 receptor inhibits NPY Y1‑mediated migration on VSMCs, PKA is involved in the signaling pathway.
血管平滑肌细胞（VSMC）的异常迁移在高血压、动脉粥样硬化和血管成形术后再狭窄中起着重要作用，这是由许多激素和体液因素调节的，包括神经肽 Y（NPY）和多巴胺。多巴胺和 NPY 都是交感神经递质，先前的一项研究表明，NPY 增加了 VSMC 的增殖，而多巴胺受体则抑制了它。因此，作者想知道多巴胺受体是否对 NPY 介导的 VSMC 迁移有抑制作用。本研究表明，NPY 刺激呈剂量依赖性（10-10-10-7 M，24 h）增加了 VSMC 的迁移，NPY 的刺激作用是通过 Y1 受体。这是因为，在 Y1 受体拮抗剂 BIBP3226（10-7 M）存在的情况下，NPY 对 VSMC 迁移的刺激作用被阻断。PD128907 对 D3 受体的激活呈剂量依赖性（10-11-10-8 M）降低了 NPY 对 VSMC 迁移的刺激作用。PD128907 的作用是通过 D3 受体，因为 D3 受体拮抗剂 U99194 阻断了 PD128907 对 NPY 介导的迁移的抑制作用。作者进一步的研究表明，D3 受体的抑制作用是通过 PKA 信号通路，在 PKA 抑制剂 14-22（10-6 M）存在的情况下，PD128907 对 VSMC 迁移的抑制作用被阻断。此外，PKA 激活剂 Sp-cAMP[S]模拟了 PD128907 的抑制作用，在 Sp-cAMP[S]存在的情况下，NPY 介导的对 VSMC 迁移的刺激作用被消除。本研究表明，D3 受体的激活抑制了 NPY Y1 介导的 VSMC 迁移，PKA 参与了信号通路。
