ATP-induced currents carried through P2X7 receptor in rat myometrial cells
Hiroshi Miyoshi1, Kaoru Yamaoka, Satoshi Urabe
1Department of Obstetrics and Gynecology, Higashihiroshima Medical Center, Higashihiroshima, Japan. miyoshi_hiroshi@hiro-hosp.jp
Objective:
The functional significance of purinergic P2 receptors in the myometrium is unclear. We previously reported the ATP-induced ionic currents in rat myometrial cells, causing uterine contractility. The aim of this study is to determine the main P2X receptors that carry the adenosine triphosphate (ATP)-induced currents.
Study Design:
We cloned predominantly expressed P2X7 receptors from rat myometrium and transfected into cultured COS-7 cells. Reconstructed P2X7 receptor currents were characterized using the whole-cell patch clamp method.
Results:
Extracellular ATP induced currents through P2X7 receptors with effective concentration (EC(50)) of 155 μmol/L, without desensitization. The myometrial P2X7 receptor was permeable to multiple monovalent cations with conductances ranked as K(+)>Cs(+)>Li(+)>Na(+). It was activated by P2X receptor agonists, with effectiveness ranked as 2',3'-O-(4-benzoylbenzoyl)-ATP (Bz-ATP)>>ATP>αβ-methylene ATP (αβ-MeATP)>2-methylthio ATP (2-MeSATP)>uridine triphosphate (UTP)>guanosine triphosphate (GTP)>adenosine diphosphate (ADP). These currents were blocked by selective P2X7 receptor antagonists and extracellular Mg(2+).
Conclusion:
P2X7 receptors carry ATP-induced currents in rat myometrial cells.
Insights
Adenosine triphosphate (ATP)-induced currents in rat myometrial cells are primarily carried by P2X7 receptors. This finding clarifies the role of purinergic signaling in uterine contractility.
Area of Science:
- Physiology
- Molecular Biology
- Pharmacology
Background:
- The role of purinergic P2 receptors in myometrial function remains largely unknown.
- Previous research indicated that adenosine triphosphate (ATP) triggers ionic currents, leading to uterine contractions.
Purpose of the Study:
- To identify the specific P2X receptors responsible for mediating ATP-induced currents in rat myometrial cells.
- To elucidate the functional significance of these receptors in uterine physiology.
Main Methods:
- Predominantly expressed P2X7 receptors were cloned from rat myometrium and transfected into COS-7 cells.
- Whole-cell patch clamp techniques were employed to characterize the reconstructed P2X7 receptor currents.
Main Results:
- Extracellular ATP induced currents via P2X7 receptors with an EC50 of 155 μmol/L, showing no desensitization.
- The P2X7 receptor exhibited permeability to various monovalent cations (K+ > Cs+ > Li+ > Na+) and was activated by specific agonists.
- These ATP-induced currents were inhibited by selective P2X7 receptor antagonists and extracellular Mg2+.
Conclusions:
- P2X7 receptors are the primary ion channels mediating ATP-induced currents in rat myometrial cells.
- This study identifies P2X7 receptors as key players in purinergic signaling within the myometrium.
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