Functional expression of purinergic P2X7 receptors in pregnant rat myometrium.
ATP has been reported to enhance the membrane conductance of myometrial cells and uterine contractility. Purinergic P2 receptor expression has been reported in the myometrium, using molecular biology, but the functional identity of the receptor subtype has not been determined. In this study, ATP-induced currents were recorded and characterized in single myometrial cells from pregnant rats using whole cell patch clamping. Extracellular ATP was applied in the range of 10 muM-1 mM and induced currents with an EC(50) of 74 muM, with no desensitization, time dependency, or voltage dependency. The currents induced carried multiple monovalent cations, with conductances ranked as K(+) > Cs(+) > Li(+) > Na(+). They were activated by P2X receptor agonists, with their effectiveness ranked as 2',3'-O-(4-benzoylbenzoyl)-ATP >> ATP > alphabeta-methylene-ATP > 2-methylthio ATP > or = UTP > or = GTP > ADP. These currents were blocked by the selective P2X7 receptor antagonist 3-[5-(2,3-dichlorophenyl)-1 H-tetrazol-1-yl]methyl pyridine (A-438079). We therefore concluded that ATP-induced currents in rat myometrial cells crossed cell membranes via P2X7 receptors. We further showed that the ATP-induced currents were blocked by extracellular Mg(2+) (IC(50) = 0.26 mM). Clinically, administering extracellular Mg(2+) is known to inhibit uterine contraction. It therefore seems likely that uterine contraction may be induced by raised extracellular ATP and suppressed via Mg(2+) inhibiting P2X7 receptors. Further research is needed into the P2X7 receptor as a therapeutic target in abnormal uterine contraction, as a possible treatment for premature labor.
Miyoshi
Hiroshi
H
Department of Obstetrics and Gynecology, Hiroshima University, Hiroshima 734-8551, Japan. hmiyoshi@hiroshima-u.ac.jp
Yamaoka
Kaoru
K
Urabe
Satoshi
S
Kodama
Miho
M
Kudo
Yoshiki
Y
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002414:Cations, Monovalent / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008274:Magnesium / Q000494:pharmacology; D009215:Myometrium / Q000187:drug effects / Q000502:physiology*; D007752:Obstetric Labor, Premature / Q000517:prevention & control; D011247:Pregnancy; D058910:Purinergic P2 Receptor Agonists; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000235:genetics* / Q000627:therapeutic use; D058486:Receptors, Purinergic P2X7; D012964:Sodium / Q000378:metabolism
D002414:Cations, Monovalent; C546470:P2rx7 protein, rat; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate; D012964:Sodium; D008274:Magnesium