作者: Harada, Tasuku ; Azuma, Yukihiro ; Hiyama, Takeshi Y ; Wada, Ikumi ; Nakamura, Kazuomi ; Nagata, Hiroki ; Hiyama, Takeshi Y. ; Xu, Shanshan ; Taniguchi, Fuminori ; Inoue, Misaki ; Yoshimura, Yuki

OBJECTIVETo evaluate the effects of a P2X4 receptor (P2X4R)-specific antagonist on murine endometriotic-like lesions and human endometriotic stromal cells.DESIGNExperimental study using an in vivo mouse endometriosis model and in vitro primary culture of human endometriotic stromal cells. NC-2600, an antagonist of the P2X4 ionotropic ATP receptor (P2X4R), was orally administered to the mice and cells. Gene expression analyses for cytokines were conducted in the endometriotic-like cysts and vaginal portion of mice, and immunohistochemistry was performed to evaluate the proliferative activity and localization of macrophages in addition to cytokine expression. The sensation of murine vaginal pain was evaluated using visceromotor responses.SETTINGThe study was performed in academic and hospital research laboratories.RESULTSNC-2600 reduced the proliferation of the cyst epithelium and vaginal pain sensation. In both cysts and vaginas, P2X4R is mainly expressed in macrophages, and NC-2600 reduces the number of tissue macrophages and reverses the elevated expression of InterleukinL-33 and cyclooxygenase-2 in animals with endometriosis.CONCLUSIONThese results indicate unknown pathophysiological roles of P2X4R expressed in local macrophages at the injury site of endometriosis and in the vagina, suggesting the potential therapeutic effects of orally administered P2X4R inhibitors for alleviating the symptoms of endometriosis.

2024-09-01·Kidney International

Platelets, inflammation, and purinergic receptors in chronic kidney disease

Review

作者: Ghanta, Sai N ; Corken, Adam L ; Jain, Nishank ; Porter, Craig ; Kore, Rajshekhar ; Rose, Shannon ; Pathak, Rupak ; Ong, Vincz ; Karaduta, Oleg

Platelets are anucleated cells that circulate in the bloodstream. Historically, platelets were thought to perform a singular function-stop bleeding via clotting. Although platelets do play a key role in hemostasis and thrombosis, recent studies indicate that platelets also modulate inflammation, and this platelet-induced inflammation contributes to the pathophysiology of various diseases such as atherosclerosis and diabetes mellitus. Thus, in recent years, our understanding of platelet function has broadened. In this review, we revisit the classic role of platelets in hemostasis and thrombosis and describe the newly recognized function of platelets in modulating inflammation. We cover the potential use of purinergic receptor antagonists to prevent platelet-modulated inflammation, particularly in patients with chronic kidney disease, and finally, we define key questions that must be addressed to understand how platelet-modulated inflammation contributes to the pathophysiology of chronic kidney disease.

2024-06-01·Physiological Reports

The role of pannexin/purinergic signaling in intervascular communication from capillaries during skeletal muscle contraction in male Golden hamsters

Article

作者: Murrant, Coral L ; Novielli-Kuntz, Nicole M ; Lamb, Iain R

AbstractWe sought to determine the physiological relevance of pannexin/purinergic‐dependent signaling in mediating conducted vasodilation elicited by capillary stimulation through skeletal muscle contraction. Using hamster cremaster muscle and intravital microscopy we stimulated capillaries through local muscle contraction while observing the associated upstream arteriole. Capillaries were stimulated with muscle contraction at low and high contraction (6 and 60CPM) and stimulus frequencies (4 and 40 Hz) in the absence and presence of pannexin blocker mefloquine (MEF; 10−5 M), purinergic receptor antagonist suramin (SUR 10−5 M) and gap‐junction uncoupler halothane (HALO, 0.07%) applied between the capillary stimulation site and the upstream arteriolar observation site. Conducted vasodilations elicited at 6CPM were inhibited by HALO while vasodilations at 60CPM were inhibited by MEF and SUR. The conducted response elicited at 4 Hz was inhibited by MEF while the vasodilation at 40 Hz was unaffected by any blocker. Therefore, upstream vasodilations resulting from capillary stimulation via muscle contraction are dependent upon a pannexin/purinergic‐dependent pathway that appears to be stimulation parameter‐dependent. Our data highlight a physiological importance of the pannexin/purinergic pathway in facilitating communication between capillaries and upstream arteriolar microvasculature and, consequently, indicating that this pathway may play a crucial role in regulating blood flow in response to skeletal muscle contraction.

项与 Purinergic P2X4 receptor antagonist(Bayer AG) 相关的新闻（医药）

2017-09-11

·BioPortfolio

Purinergic Receptor Purinoceptor Antagonist Pipeline Insights, 2017 [Report Updated: 01092017] Prices from USD $1250

DelveInsight's, Purinergic Receptor Purinoceptor AntagonistMechanism of action Insights, 2017, report provides comprehensive insights of the ongoing therapeutic research and development across Purinergic Receptor Purinoceptor Antagonist. The report provides a complete understanding of the pipeline activities covering all clinical, preclinical and discovery stage products. A comparative pipeline therapeutics assessment of Purinergic Receptor Purinoceptor Antagonist by development stage, therapy type, route of administration and molecule type is also covered in the report. It also has a special feature on the inactive pipeline products in this area. The report is built using data and information sourced from proprietary databases, primary and secondary research and inhouse analysis by DelveInsights team of industry experts. Secondary sources information and data has been collected from various printable and nonprintable sources like search engines, News websites, Government Websites, Trade Journals, White papers, Magazines, Trade associations, Books, Industry Portals, Industry Associations and access to available databases. Scope of the report The report provides a snapshot of the pipeline development for the Purinergic Receptor Purinoceptor Antagonist The report covers pipeline activity across the complete product development cycle i.e. clinical, preclinical and discovery stages for the Purinergic Receptor Purinoceptor Antagonist The report provides pipeline product profiles which includes product description, developmental activities, licensors collaborators and chemical information Provides pipeline assessment by monotherapy and combination therapy products, stage of development, route of administration, and molecule type for Purinergic Receptor Purinoceptor Antagonist The report also covers the dormant and discontinued pipeline projects related to the Purinergic Receptor Purinoceptor Antagonist Reasons to Buy Establish comprehensive understanding of the pipeline activity across this Purinergic Receptor Purinoceptor Antagonist to formulate effective RD strategies Gather information of the emerging competitors having potentially lucrative portfolio in this space and create effective counter strategies to gain competitive advantage Plot corrective measures for pipeline projects by understanding the pipeline depth and focus of Purinergic Receptor Purinoceptor Antagonist therapeutics Devise in licensing and out licensing strategies by identifying prospective partners with the most attractive projects to enhance and expand business potential and scope Modify the therapeutic portfolio by identifying inactive projects and understanding the factors that might have halted their progress

100 项与 Purinergic P2X4 receptor antagonist(Bayer AG) 相关的药物交易

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