ArticleJournal of neuroendocrinology2021
Neurolysin substrates bradykinin, neurotensin and substance P enhance brain microvascular permeability in a human in vitro model.
Article in Journal of neuroendocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Vascular Endothelial Barrier in Salivary Glands: From Physiological Regulation to Pathological Impairment of Secretion.International journal of molecular sciences · 2026Review
- Discovery of a pyridine-piperazine-based small molecule that enhances the activity of peptidase neurolysin.The Journal of pharmacology and experimental therapeutics · 2026Article
- Reversibly unlocking the blood-brain barrier: A study on microtubule dynamics modulation using gold nanoparticle-modified reduced graphene oxide.Acta pharmaceutica Sinica. B · 2026Article
- Neurotensin Regulates Primate Ovulation Via Multiple Neurotensin Receptors.Endocrinology · 2025Article
- Cellular metabolism of substance P produces neurokinin-1 receptor peptide agonists with diminished cyclic AMP signaling.American journal of physiology. Cell physiology · 2024Article
- Imidazole Bioisostere Activators of Endopeptidase Neurolysin with Enhanced Potency and Metabolic Stability.ACS medicinal chemistry letters · 2024Article
- A circadian clock regulates the blood-brain barrier across phylogeny.Vitamins and hormones · 2024Review
- The Role of Induced Pluripotent Stem Cells in the Treatment of Stroke.Current neuropharmacology · 2024Review
- Discovery of the Next Generation of Non-peptidomimetic Neurolysin Activators with High Blood-Brain Barrier Permeability: a Pharmacokinetics Study in Healthy and Stroke Animals.Pharmaceutical research · 2023Article
- Development of fluorogenic substrates for colorectal tumor-related neuropeptidases for activity-based diagnosis.Chemical science · 2023Article
- The relationship between dietary total antioxidant capacity, clinical parameters, and oxidative stress in fibromyalgia syndrome: A novel point of view.Turkish journal of physical medicine and rehabilitation · 2022Article
- Small molecule neurolysin activators, potential multi-mechanism agents for ischemic stroke therapy.Expert opinion on therapeutic targets · 2022Article
- Bradykinin-target therapies in SARS-CoV-2 infection: current evidence and perspectives.Naunyn-Schmiedeberg's archives of pharmacology · 2022Review
- Potentials of Neuropeptides as Therapeutic Agents for Neurological Diseases.Biomedicines · 2022Review
- Identification and Characterization of Two Structurally Related Dipeptides that Enhance Catalytic Efficiency of Neurolysin.The Journal of pharmacology and experimental therapeutics · 2021Article
- Discovery of First-in-Class Peptidomimetic Neurolysin Activators Possessing Enhanced Brain Penetration and Stability.Journal of medicinal chemistry · 2021Article
- Between two storms, vasoactive peptides or bradykinin underlie severity of COVID-19?Physiological reports · 2021Review
- Modeling the blood-brain barrier for treatment of central nervous system (CNS) diseases.Journal of tissue engineeringReview
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Increased brain microvascular permeability and disruption of blood-brain barrier (BBB) function are among hallmarks of several acute neurodegenerative disorders, including stroke. Numerous studies suggest the involvement of bradykinin (BK), neurotensin (NT) and substance P (SP) in BBB impairment and oedema formation after stroke; however, there is paucity of data in regard to the direct effects of these peptides on the brain microvascular endothelial cells (BMECs) and BBB. The present study aimed to evaluate the direct effects of BK, NT and SP on the permeability of BBB in an in vitro model based on human induced pluripotent stem cell (iPSC)-derived BMECs. Our data indicate that all three peptides increase BBB permeability in a concentration-dependent manner in an in vitro model formed from two different iPSC lines (CTR90F and CTR65M) and widely used hCMEC/D3 human BMECs. The combination of BK, NT and SP at a sub-effective concentration also resulted in increased BBB permeability in the iPSC-derived model indicating potentiation of their action. Furthermore, we observed abrogation of BK, NT and SP effects with pretreatment of pharmacological blockers targeting their specific receptors. Additional mechanistic studies indicate that the short-term effects of these peptides are not mediated through alteration of tight-junction proteins claudin-5 and occludin, but likely involve redistribution of F-actin and secretion of vascular endothelial growth factor. This is the first experimental study to document the increased permeability of the BBB in response to direct action of NT in an in vitro model. In addition, our study confirms the expected but not well-documented, direct effect of SP on BBB permeability and adds to the well-recognised actions of BK on BBB. Lastly, we demonstrate that peptidase neurolysin can neutralise the effects of these peptides on BBB, suggesting potential therapeutic implications.
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