Inhibitory effect of D1-like dopamine receptors on neuropeptide Y-induced proliferation in vascular smooth muscle cells

Abstract

Proliferation of vascular smooth muscle cells (VSMCs) is thought to have a key role in the development of atherosclerotic lesions. Neuropeptide Y (NPY), norepinephrine and dopamine are sympathetic neurotransmitters. NPY has been particularly shown to stimulate proliferation of VSMCs. NPY, norepinephrine and dopamine are all sympathetic transmitters. In our previous study, we found that in the presence of the dopamine receptor, the α1-adrenergic receptor-mediated VSMC proliferation is reduced. We hypothesize that the activation of the D1-like receptor might inhibit the NPY-mediated VSMC proliferation. In our present study, we found that NPY, mainly via the Y1 receptor, increased VSMC proliferation. This was determined by [(3)H]-thymidine incorporation, in a concentration (10(-11) to 10(-8) M)-dependent manner. In the presence of the D1-like receptor agonist, fenoldopam (10(-12) to 10(-5) M), the stimulatory effect of NPY on VSMC proliferation was reduced. The involvement of the D1-like receptor was confirmed when the inhibitory effect of fenoldopam was reversed in the presence of the D1-like receptor antagonist SCH-23390 (10(-8) M). Moreover, the inhibitory effect of fenoldopam on NPY-mediated VSMC proliferation was also blocked in the presence of the PKA inhibitor 14-22 (10(-6) M). Protein kinase A activator 8-(4-chlorophenylthio) adenosine-3,5-cyclic monophosphorothioate, Sp-isomer sodium salt (10(-6) M) could simulate the stimulatory effect of fenoldopam. It indicated that the inhibitory effect of D1-like receptors on NPY-mediated VSMC proliferation may have an important role in the regulation of blood pressure or prevention of atherosclerosis.

Inhibitory effect of D3 dopamine receptors on neuropeptide Y-induced migration in vascular smooth muscle cells

“…Dopamine and NPY are both sympathetic neurotransmitters, but dopamine has a significant anti-hypertensive and anti-atherosclerotic effect (15,16). Previous studies of the authors reported that activation of dopamine receptor inhibits norepinephrine-mediated VSMC proliferation (10,17), a similar inhibitory effect of dopamine on NPY-mediated VSMC proliferation was also observed. The authors intended to understand whether or not there is an inhibitory effect of dopamine receptor on NPY-mediated VSMC migration.…”

“…1B, the effect of NPY was largely but not completely blocked, indicating that other NPY receptors may also contribute to the migration. In the VSMC, Y2 and Y5 also engaged in NPY-induced migration (10), but Y 1 was the main vascular receptor (40,41).…”

“…Cell culture. VSMCs were isolated from the aortic strips of male Sprague-Dawley rats weighing 200-250 g with an implant technique previously described (10). This experiment was approved by the Third Military Medical University Animal Use and Care Committee (Chongqing, China).…”

“…NPY has both potent central and peripheral biological effects, including cardiovascular actions, which participate in the development of cardiovascular diseases. There are also reports indicating that NPY receptor existed in VSMCs, and that stimulation of VSMCs with NPY increased VSMC proliferation and migration (8)(9)(10). In hypertension or atherosclerosis, NPY-mediated migration of VSMCs is augmented (11).…”

Segregated Nanocompartments Containing Therapeutic Enzymes and Imaging Compounds within DNA‐Zipped Polymersome Clusters for Advanced Nanotheranostic Platform

“…[39] Dopamine is a key factor in atherosclerosis prevention, [40] regulating vascular dynamics by activation of dopaminergic receptor D1 (DRD1). [41][42][43] Atherosclerosis is characterized by plaque buildup in the arteries, restricting blood flow. It often has no symptoms until a life-threatening event such as a heart attack or stroke occurs, highlighting the need for early prevention and detection.…”