Last update 01 Nov 2024

P2X1 receptor

Last update 01 Nov 2024

Basic Info

Synonyms

ATP receptor, P2RX1, P2X purinoceptor 1

+ [4]

Introduction

Ligand-gated ion channel with relatively high calcium permeability. Binding to ATP mediates synaptic transmission between neurons and from neurons to smooth muscle. Seems to be linked to apoptosis, by increasing the intracellular concentration of calcium in the presence of ATP, leading to programmed cell death (By similarity).

Drugs associated with P2X1 receptor

Aurintricarboxylic

Target

P2X1 receptor x P2X3 receptor

Mechanism

P2X1 receptor antagonists [+1]

Active Org.

RWTH Aachen University

Originator Org.

RWTH Aachen University

Active Indication

Chronic cough [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

MRS-2220

Target

P2X1 receptor

Mechanism

P2X1 receptor antagonists

Active Org.-

Originator Org.

National Institutes of Health

Active Indication-

Inactive Indication

Hypertension [+1]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

MRS-2142

Target

P2X1 receptor

Mechanism

P2X1 receptor antagonists

Active Org.-

Originator Org.

National Institutes of Health

Active Indication-

Inactive Indication-

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with P2X1 receptor

100 Translational Medicine associated with P2X1 receptor

0 Patents (Medical) associated with P2X1 receptor

936

Literatures (Medical) associated with P2X1 receptor

01 Dec 2024·Biomedical Journal

Altered purinergic P2X7 and A2B receptors signaling limits macrophage-mediated host defense in schistosomiasis

Article

Author: Monteiro, Matheus Macedo L V ; Thorstenberg, Maria Luiza ; Pereira, HenriqueM Gualberto ; Oliveira, Nathália Ferreira ; Santos, GustavoR C ; Savio, Luiz Eduardo Baggio ; Silva, Claudia Lucia Martins ; Martins, Monique Daiane Andrade ; Coutinho-Silva, Robson

BACKGROUNDThe occurrence of co-infections during schistosomiasis, a neglected tropical disease, with other parasites have been reported suggesting an impaired host immune defense. Macrophage purinergic P2X7 receptor (P2X7R) play an important role against intracellular pathogens. Therefore, we investigated the P2X7R-mediated phagocytosis and killing capacity of Leishmania amazonensis by macrophages during schistosomiasis in vitro and in vivo.METHODSSwiss and C57BL/6 (Wild type) and P2X7R^-/- were randomized in two groups: control (uninfected) and Schistosoma mansoni-infected. Alternatively, control Swiss and S. mansoni-infected mice were also infected with L. amazonensis.RESULTSThe pre-treatment of macrophages with the P2X7R antagonist (A74003) or TGF-β reduced the phagocytosis index, mimicking the phenotype of cells from S. mansoni-infected mice and P2X7R^-/- mice. Apyrase also reduced the phagocytosis index corroborating the role of ATP to macrophage activation. Moreover, l-arginine-nitric oxide pathway was compromised, which could explain the reduced killing capacity in response to ATP in vitro and in vivo. We found an increased extracellular nucleotide (ATP, ADP and AMP) hydrolysis along with an increased frequency of F4/80⁺ CD39⁺ macrophages from the S. mansoni-infected group. Moreover, the content of adenosine in the cell supernatant was higher in the S. mansoni-infected group in relation to controls. Schistosomiasis also increased the expression of macrophage adenosine A_2BR. In good accordance, both ADA and the selective A_2BR antagonist restored the phagocytosis index of macrophages from S. mansoni-infected group.CONCLUSIONSAltogether, the altered P2X7R and A_2BR signaling limits the role of macrophages to host defense against L. amazonensis during schistosomiasis, potentially contributing to the pathophysiology and clinically relevant co-infections.

01 Oct 2024·Pflügers Archiv - European Journal of Physiology

Stress-induced impairment of parasympathetic NO-mediated inhibition of sympathetic vasoconstriction in submucosal arteriole of rat rectum

Article

Author: Mitsui, Retsu ; Hashitani, Hikaru ; Yamori, Mizuki ; Nakamori, Hiroyuki

In the gastrointestinal tract, nitrergic inhibition of the arteriolar contractility has not been demonstrated. Here, we explored whether neurally-released nitric oxide (NO) inhibits sympathetic vasoconstrictions in the rat rectal arterioles. Changes in sympathetic vasoconstrictions and their nitrergic modulation in rats exposed to water avoidance stress (WAS, 10 days, 1 h per day) were also examined. In rectal submucosal preparations, changes in arteriolar diameter were monitored using video microscopy. In control or sham-treated rats, electrical field stimulation (EFS)-induced sympathetic vasoconstrictions were increased by the neuronal nitric oxide synthase (nNOS) inhibitor L-NPA (1 μM) and diminished by the cyclic guanosine monophosphate-specific phosphodiesterase 5 (PDE5) inhibitor tadalafil (10 nM). In phenylephrine-constricted, guanethidine-treated arterioles, EFS-induced vasodilatations were inhibited by the calcitonin gene-related peptide (CGRP) receptor antagonist BIBN-4096 (1 μM) but not L-NPA. Perivascular nNOS-immunoreactive nitrergic fibres co-expressing the parasympathetic marker vesicular acetylcholine transporter (VAChT) were intermingled with tyrosine hydroxylase (TH)-immunoreactive sympathetic fibres expressing soluble guanylate cyclase (sGC), a receptor for NO. In WAS rats in which augmented sympathetic vasoconstrictions were developed, L-NPA failed to further increase the vasoconstrictions, while tadalafil-induced inhibition of the vasoconstrictions was attenuated. Phenylephrine- or α,β-methylene ATP-induced vasoconstrictions and acetylcholine-induced vasodilatations were unaltered by WAS. Thus, in arterioles of the rat rectal submucosa, NO released from parasympathetic nerves appears to inhibit sympathetic vasoconstrictions presumably by reducing sympathetic transmitter release. In WAS rats, sympathetic vasoconstrictions are augmented at least partly due to the diminished pre-junctional nitrergic inhibition of transmitter release without changing α-adrenoceptor or P2X-purinoctor mediated vasoconstriction and endothelium-dependent vasodilatation.

01 Oct 2024·Journal of Dermatological Science

P2X7R-primed keratinocytes are susceptible to apoptosis via GPCR-Gβγ-pERK signal pathways

Article

Author: Hasegawa, Akito ; Nishiguchi, Tomoki ; Ozawa, Takeaki ; Abe, Riichiro ; Kimura, Haruna ; Saito, Yuki

BACKGROUNDCell death constitutes a pivotal biological phenomenon essential for the preservation of homeostasis within living organisms. In the context of maintaining a functional skin barrier, keratinocytes exert positively and negatively control cell death signals. However, in patients with severe drug eruptions, anomalous overexpression of the formyl peptide receptor 1 (FPR1) in keratinocytes elicits a distinctive mode of cell death known as necroptosis, thereby suffering a loss of the skin barrier. The precise molecular mechanisms connecting FPR1 activation to this cell death remain unclear.OBJECTIVEWe have investigated the intracellular signal transduction cascade governing FPR1-mediated cell death in cultured keratinocytes.METHODSWe used HaCaT cells as a model keratinocyte. The expression of FPR1 was detected with qPCR. The presence of cell death events was monitored through live-cell fluorescent staining and LDH release assays. Furthermore, the phosphorylation of ERK was assessed via Western blot analysis. Intracellular signal pathways were investigated using specific inhibitors.RESULTSLigand stimulation of an endogenous ion channel, purinergic receptor P2X7 (P2X7R), increased the FPR1 expression level. This upregulated FPR1 demonstrated functional competence in the phosphorylation of downstream MAP kinase and the initiation of cell death. Notably, this cell death was ameliorated upon the administration of inhibitors targeting Gβγ, ERK, and caspases.CONCLUSIONThe induction and stimulation of FPR1 initiated apoptosis in keratinocytes via the Gβγ-pERK signaling pathway. Our findings postulate that the downstream components of FPR1 represent an alternative therapeutic target for preventing unintended keratinocyte cell death.

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P2X1 receptor

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