Inhibitory effect of D3 dopamine receptors on neuropeptide Y-induced migration in vascular smooth muscle cells
Molecular Medicine Reports
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
... inhibitory effect of dopamine receptor on NPY-mediated VSMC migration. The present study demonstrated that stimulation with NPY dose-dependence (10 -10 -10 -7 M, 24 h) increased VSMC migration, the stimulatory effect of NPY was via the Y 1 receptor. This is because, in the presence of the Y 1 receptor antagonist, BIBP3226 (10 -7 M), the stimulatory effect of NPY on VSMC migration was blocked. Activation of the D 3 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 D 3 receptor, because the inhibitory effect of PD128907 on NPY-mediated migration was blocked by the D 3 receptor antagonist, U99194. The authors' further study suggested that the inhibitory effect of the D 3 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 D 3 receptor inhibits NPY Y 1 -mediated migration on VSMCs, PKA is involved in the signaling pathway.