ArticleCanadian journal of physiology and pharmacology2008
Interactions of multiple signaling pathways in neuropeptide Y-mediated bimodal vascular smooth muscle cell growth.
Article in Canadian journal of physiology and pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Neuropeptide Y in cancer metastasis and chemoresistance.Neuropeptides · 2026Review
- Effects of Mytilus edulis derived plasmalogens against atherosclerosis via lipid metabolism and MAPK signaling pathway.NPJ science of food · 2025Article
- Mechanism of action of exercise regulating intestinal microflora to improve spontaneous hypertension in rats.Biomolecules & biomedicine · 2025Article
- Neuropeptide Y in cancer-biological functions and potential clinical implications.Cancer metastasis reviews · 2025Review
- Physiology of the tongue with emphasis on taste transduction.Physiological reviews · 2023Review
- Neuropeptide Y Promotes Human M2 Macrophage Polarization and Enhances p62/SQSTM1-Dependent Autophagy and NRF2 Activation.International journal of molecular sciences · 2022Article
- Immunomodulatory Role of Neuropeptides in the Cornea.Biomedicines · 2022Review
- Hypoxia-activated neuropeptide Y/Y5 receptor/RhoA pathway triggers chromosomal instability and bone metastasis in Ewing sarcoma.Nature communications · 2022Article
- Review
- Neuropeptide Y/Y5 Receptor Pathway Stimulates Neuroblastoma Cell Motility Through RhoA Activation.Frontiers in cell and developmental biology · 2020Article
- Turning the 'Tides on Neuropsychiatric Diseases: The Role of Peptides in the Prefrontal Cortex.Frontiers in behavioral neuroscience · 2020Article
- Neuropeptide Y receptor interactions regulate its mitogenic activity.Neuropeptides · 2019Article
- Platelet Lysate-Derived Neuropeptide y Influences Migration and Angiogenesis of Human Adipose Tissue-Derived Stromal Cells.Scientific reports · 2018Article
- Different effects of neuropeptide Y on proliferation of vascular smooth muscle cells via regulation of Geminin.Molecular and cellular biochemistry · 2017Article
- Neuropeptide Y (NPY) in tumor growth and progression: Lessons learned from pediatric oncology.Neuropeptides · 2016Review
- Boolean Modeling Reveals the Necessity of Transcriptional Regulation for Bistability in PC12 Cell Differentiation.Frontiers in genetics · 2016Article
- Inhibitory effect of D1-like dopamine receptors on neuropeptide Y-induced proliferation in vascular smooth muscle cells.Hypertension research : official journal of the Japanese Society of Hypertension · 2015Article
- Neuropeptide Y receptor Y5 as an inducible pro-survival factor in neuroblastoma: implications for tumor chemoresistance.Oncogene · 2015Article
- NPY/Y₁ receptor-mediated vasoconstrictory and proliferative effects in pulmonary hypertension.British journal of pharmacology · 2014Article
- Hypoxia shifts activity of neuropeptide Y in Ewing sarcoma from growth-inhibitory to growth-promoting effects.Oncotarget · 2013Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Neuropeptide Y (NPY), a sympathetic cotransmitter, acts via G protein-coupled receptors to stimulate constriction and vascular smooth muscle cell (VSMC) proliferation through interactions with its Y1 receptors. However, VSMC proliferation appears bimodal, with high- and low-affinity peaks differentially blocked by antagonists of both Y1 and Y5 receptors. Here, we sought to determine the signaling mechanisms of NPY-mediated bimodal mitogenesis. In rat aortic VSMCs, NPY's mitogenic effect at all concentrations was blocked by pertussis toxin and was associated with decreased forskolin-stimulated cAMP levels. NPY also increased intracellular calcium levels; in contrast to mitogenesis, this effect was dose dependent. The rise in intracellular Ca2+ depended on extracellular Ca2+ and was mediated via activation of Y1 receptors, but not Y5 receptors. Despite differences in calcium, the signaling pathways activated at low and high NPY concentrations were similar. The mitogenic effect of the peptide at all doses was completely blocked by inhibitors of calcium/calmodulin-dependent kinase II (CaMKII), protein kinase C (PKC), and mitogen-activated protein kinase kinase, MEK1/2. Thus, in VSMCs, NPY-mediated mitogenesis signals primarily via Y1 receptors activating 2 Ca2+-dependent, growth-promoting pathways -- PKC and CaMKII. At the high-affinity peak, these 2 pathways are amplified by Y5 receptor-mediated, calcium-independent inhibition of the adenylyl cyclase - protein kinase A (PKA) pathway. All 3 mechanisms converge to the extracellular signal-regulated kinases (ERK1/2) signaling cascade and lead to VSMC proliferation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.