Last update 01 Nov 2024

PGE2 x calcium channel

Last update 01 Nov 2024

Basic Info

Related Targets

PGE2calcium channel

Drugs associated with PGE2 x calcium channel

L-366682

Target

PGE2 x calcium channel

Mechanism

PGE2 antagonists [+1]

Active Org.-

Originator Org.

Merck & Co., Inc.

Active Indication-

Inactive Indication

Obstetric Labor, Premature

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PGE2 x calcium channel

100 Translational Medicine associated with PGE2 x calcium channel

0 Patents (Medical) associated with PGE2 x calcium channel

Literatures (Medical) associated with PGE2 x calcium channel

01 May 2024·Journal of Ethnopharmacology

Schisandrin B from Schisandra chinensis alleviated pain via glycine receptors, Nav1.7 channels and Cav2.2 channels

Article

Author: Wu, Jun ; Jin, Yuchen ; Li, Min ; Yu, KeXin ; Yu, Haibo ; Zhao, Miao

ETHNOPHARMACOLOGICAL RELEVANCESchisandra chinensis, the dried and ripe fruit of the magnolia family plant Schisandra chinensis (Turcz.) Baill, was commonly used in traditional analgesic prescription. Studies have shown that the extract of Schisandra chinensis (SC) displayed analgesic activity. However, the analgesic active component and the exact mechanisms have yet to be revealed.AIM OF THE STUDYThe present study was to investigate the anti-nociceptive constituent of Schisandra chinensis, assess its analgesic effect, and explore the potential molecular mechanisms.MATERIALS AND METHODSThe effects of a series of well-recognized compounds from SC on glycine receptors were investigated. The analgesic effect of the identified compound was evaluated in three pain models. Mechanistic studies were performed using patch clamp technique on various targets expressed in recombinant cells. These targets included glycine receptors, Nav1.7 sodium channels, Cav2.2 calcium channels et al. Meanwhile, primary cultured spinal dorsal horn (SDH) neurons and dorsal root ganglion (DRG) neurons were also utilized.RESULTSSchisandrin B (SchB) was a positive allosteric modulator of glycine receptors in spinal dorsal horn neurons. The EC₅₀ of SchB on glycine receptors in spinal dorsal horn neurons was 2.94 ± 0.28 μM. In three pain models, the analgesic effect of SchB was comparable to that of indomethacin at the same dose. Besides, SchB rescued PGE₂-induced suppression of α3 GlyR activity and alleviated persistent pain. Notably, SchB could also potently decrease the frequency of action potentials and inhibit sodium and calcium channels in DRG neurons. Consistent with the data from DRG neurons, SchB was also found to significantly block Nav1.7 sodium channels and Cav2.2 channels in recombinant cells.CONCLUSIONOur results demonstrated that, Schisandrin B, the primary lignan component of Schisandra chinensis, may exert its analgesic effect by acting on multiple ion channels, including glycine receptors, Nav1.7 channels, and Cav2.2 channels.

09 Mar 2023·Metabolites

Multi-Omics Analysis of Lung Tissue Demonstrates Changes to Lipid Metabolism during Allergic Sensitization in Mice.

Article

Author: Bauer, Alison K. ; Manke, Jonathan ; Reisdorph, Nichole ; Michel, Cole R. ; Doenges, Katrina A. ; Turi, Kedir N.

Allergy and asthma pathogenesis are associated with the dysregulation of metabolic pathways. To understand the effects of allergen sensitization on metabolic pathways, we conducted a multi-omics study using BALB/cJ mice sensitized to house dust mite (HDM) extract or saline. Lung tissue was used to perform untargeted metabolomics and transcriptomics while both lung tissue and plasma were used for targeted lipidomics. Following statistical comparisons, an integrated pathway analysis was conducted. Histopathological changes demonstrated an allergic response in HDM-sensitized mice. Untargeted metabolomics showed 391 lung tissue compounds were significantly different between HDM and control mice (adjusted p < 0.05); with most compounds mapping to glycerophospholipid and sphingolipid pathways. Several lung oxylipins, including 14-HDHA, 8-HETE, 15-HETE, 6-keto-PGF1α, and PGE2 were significantly elevated in HDM-sensitized mice (p < 0.05). Global gene expression analysis showed upregulated calcium channel, G protein-signaling, and mTORC1 signaling pathways. Genes related to oxylipin metabolism such as Cox, Cyp450s, and cPla2 trended upwards. Joint analysis of metabolomics and transcriptomics supported a role for glycerophospholipid and sphingolipid metabolism following HDM sensitization. Collectively, our multi-omics results linked decreased glycerophospholipid and sphingolipid compounds and increased oxylipins with allergic sensitization; concurrent upregulation of associated gene pathways supports a role for bioactive lipids in the pathogenesis of allergy and asthma.

01 Jan 2023·Biochemical and Biophysical Research Communications

Opioid modulation of T-type Ca2+ channel-dependent neuritogenesis/neurite outgrowth through the prostaglandin E2/EP4 receptor/protein kinase A pathway in mouse dorsal root ganglion neurons

Article

Author: Tsubota, Maho ; Yamagata, Ryosuke ; Yoshida, Shigeru ; Mitani, Kenji ; Kawabata, Atsufumi ; Sekiguchi, Fumiko ; Maeda, Takashi

Irregular regeneration or inappropriate remodeling of the axons of the primary afferent neurons after peripheral nerve trauma could be associated with the development of neuropathic pain. We analyzed the molecular mechanisms for the neuritogenesis and neurite outgrowth caused by prostaglandin E₂ (PGE₂) in mouse dorsal root ganglion (DRG) neurons, and evaluated their opioid modulation. PGE₂ in combination with IBMX, a phosphodiesterase inhibitor, caused neuritogenesis/neurite outgrowth in DRG cells, an effect abolished by a prostanoid EP₄, but not EP₂, receptor antagonist, and inhibitors of adenylyl cyclase or protein kinase A (PKA). Blockers of T-type Ca²⁺ channels (T-channels), that are responsible for window currents involving the sustained low-level Ca²⁺ entry at voltages near the resting membrane potentials and can be functionally upregulated by PKA, inhibited the neuritogenesis/neurite outgrowth caused by PGE₂/IBMX or dibutylyl cyclic AMP, a PKA activator, in DRG neurons, an inhibitory effect mimicked by ZnCl₂ and ascorbic acid that block Ca_v3.2, but not Ca_v3.1 or Ca_v3.3, T-channels. Morphine and DAMGO, μ-opioid receptor (MOR) agonists, suppressed the neuritogenesis and/or neurite outgrowth induced by PGE₂/IBMX in DRG neurons and also DRG neuron-like ND7/23 cells, an effect reversed by naloxone or β-funaltrexamine, a selective MOR antagonist. Our data suggest that the EP₄ receptor/PKA/Ca_v3.2 pathway is involved in the PGE₂-induced neuritogenesis/neurite outgrowth in DRG neurons, which can be suppressed by MOR stimulation. We propose that MOR agonists including morphine in the early phase after peripheral nerve trauma might delay the axonal regeneration of the primary afferent neurons but prevent the development of neuropathic pain.

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