The expression levels of P2X purinergic receptors were determined in the myometrium of pregnant rats using the quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). The messenger RNAs (mRNAs) of P2X4 and P2X7 were expressed most strongly. The expression levels of these receptors increased during the late stages of pregnancy; at the time of delivery, the mRNA levels of P2X4 and P2X7 had increased to 1.9 and 3.2 times the day 19 values, respectively. We also explored the roles of P2X receptors in hormone-induced and inflammation-induced preterm delivery models. In the former, mifepristone caused the P2X4 and P2X7 mRNA levels to increase to 2.1 and 4.1 times the control values, respectively. In the latter, lipopolysaccharide (LPS) caused the mRNA levels of P2X4 and P2X7 to increase dramatically to 7.4 and 18.6 times the control values, respectively. These findings suggest that increased P2X4 and P2X7 receptor expression in pregnant rats is related to uterine contraction leading to term and preterm delivery.
Garfield RE, Sims S., Daniel EEGap junctions: their presence and necessity in myometrium during parturition . Science. 1977;198(4320):958-960.
2.
Soloff MS, Alexandrova M., Fernstrom MJOxytocin receptors: triggers for parturition and lactation? Science. 1979; 204(4399):1313-1315.
3.
Carsten ME, Miller JDA new look at uterine muscle contraction. Am J Obstet Gynecol . 1987;157(5):1303-1315.
4.
Sanborn BMRelationship of ion channel activity to control of myometrial calcium. J Soc Gynecol Investig. 2000;7(1):4-11.
5.
Wray S.Uterine contraction and physiological mechanisms of modulation. Am J Physiol. 1993;264(1 pt 1):C1-C18.
6.
Inoue R., Isenberg G.Intracellular calcium ions modulate acetylcholine-induced inward current in guinea-pig ileum. J Physiol. 1990;424:73-92.
7.
Janssen LJ, Sims SMAcetylcholine activates non-selective cation and chloride conductances in canine and guinea-pig tracheal myocytes. J Physiol. 1992:453:197-218.
8.
Sims SMCholinergic activation of a non-selective cation current in canine gastric smooth muscle is associated with contraction. J Physiol. 1992;449:377-398.
9.
Vogalis F., Sanders KMCholinergic stimulation activates a non-selective cation current in canine pyloric circular muscle cells. J Physiol. 1990;429:223-236.
10.
Bae YM, Park MK, Lee SH, Ho WK, Earm YEContribution of Ca2+-activated K+ channels and non-selective cation channels to membrane potential of pulmonary arterial smooth muscle cells of the rabbit . J Physiol. 1999;514(pt 3):747-758.
11.
Miyoshi H., Yamaoka K., Garfield RE, Ohama K.Identification of a non-selective cation channel current in myometrial cells isolated from pregnant rats. Pflugers Arch. 2004;447(4): 457-464.
12.
Babich LG, Ku CY, Young HW, Huang H., Blackburn MR, Sanborn BMExpression of capacitative calcium TrpC proteins in rat myometrium during pregnancy. Biol Reprod. 2004;70(4):919-924.
13.
Honore E., Martin C., Mironneau C., Mironneau J.An ATP-sensitive conductance in cultured smooth muscle cells from pregnant rat myometrium. Am J Physiol. 1989;257(2 pt 1): C297-C305.
14.
Ninomiya JG, Suzuki H.Electrical responses of smooth muscle cells of the mouse uterus to adenosine triphosphate. J Physiol. 1983;342:499-515.
15.
Romero R., Mazor M.Infection and preterm labor. Clin Obstet Gynecol. 1988;31(3):553-584.
16.
Fidel PL Jr , Romero R., Wolf N., et al. Systemic and local cytokine profiles in endotoxin-induced preterm parturition in mice. Am J Obstet Gynecol. 1994;170(5 pt 1):1467-1475.
17.
Okawa T., Suzuki H., Yaanagida K., et al. Effect of lipopolysaccharide on uterine contractions and prostaglandin production in pregnant rats. Am J Obstet Gynecol. 2001;184(2): 84-89.
18.
Miyoshi H., Boyle MB, MacKay LB, Garfield REVoltage-clamp studies of gap junctions between uterine muscle cells during term and preterm labor. Biophys J. 1996;71(3): 1324-1334.
19.
Doret M., Bukowski R., Longo M., et al. Uterine electromyography characteristics for early diagnosis of mifepristone-induced preterm labor. Obstet Gynecol. 2005;105(4): 822-830.
20.
Friel DDAn ATP-sensitive conductance in single smooth muscle cells from the rat vas deferens. J Physiol. 1988;401: 361-380.
21.
Benham CD, Tsien RWA novel receptor-operated Ca2+permeable channel activated by ATP in smooth muscle. Nature. 1987;328(6127):275-278.
22.
Vial C., Evans RJP2X receptor expression in mouse urinary bladder and the requirement of P2X(1) receptors for functional P2X receptor responses in the mouse urinary bladder smooth muscle. Br J Pharmacol. 2000;131(7):1489-1495.
23.
Gillman TA, Pennefather JNEvidence for the presence of both P1 and P2 purinoceptors in the rat myometrium . Clin Exp Pharmacol Physiol. 1998;25(7-8):592-599.
24.
Bo X., Kim M., Nori SL, Schoepfer R., Burnstock G., North RATissue distribution of P2X4 receptors studied with an ectodomain antibody . Cell Tissue Res. 2003;313(2): 159-165.
25.
Egan TM, Khakh BSContribution of calcium ions to P2X channel responses. J Neurosci . 2004;24(13):3413-3420.
26.
Lee HK, Ro S., Keef KD, et al. Differential expression of P2Xpurinoceptor subtypes in circular and longitudinal muscle of canine colon. Neurogastroenterol Motil. 2005;17(4):575-584.
27.
Tsuda M., Shigemoto-Mogami Y., Koizumi S., et al. P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature. 2003;424(6950):778-783.
28.
Yamamoto K. , Sokabe T., Matsumoto TY, et al. Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice. Nat Med . 2006;12(1):133-137.
29.
Valdecantos P., Briones R., Moya P., Germain A., Huidobro-Toro JPPharmacological identification of P2X1, P2X4 and P2X7 nucleotide receptors in the smooth muscles of human umbilical cord and chorionic blood vessels. Placenta. 2003 ; 24(1):17-26.
30.
Ferrari D., Villalba M., Chiozzi P., Falzoni S., Ricciardi-Castagnoli P., Di Virgilio F.Mouse microglial cells express a plasma membrane pore gated by extracellular ATP. J Immunol. 1996;156(4):1531-1539.
31.
Wang Q., Wang L., Feng YH, Li X., Zeng R., Gorodeski GIP2X7 receptor-mediated apoptosis of human cervical epithelial cells. Am J Physiol Cell Physiol. 2004;287(5):C1349-C1358.
32.
Mershon JL, Mikala G., Schwartz A.Changes in the expression of the L-type voltage-dependent calcium channel during pregnancy and parturition in the rat. Biol Reprod. 1994; 51(5):993-999.
33.
Miller SM, Garfield RE, Daniel EEImproved propagation in myometrium associated with gap junctions during parturition . Am J Physiol. 1989;256(1 pt 1):C130-C141.
34.
Lye SJ, Nicholson BJ, Mascarenhas M., MacKenzie L., Petrocelli T.Increased expression of connexin-43 in the rat myometrium during labor is associated with an increase in the plasma estrogen:progesterone ratio. Endocrinology. 1993;132(6): 2380-2386.
35.
Tezuka N., Ali M., Chwalisz K., Garfield REChanges in transcripts encoding calcium channel subunits of rat myometrium during pregnancy. Am J Physiol. 1995;269(4 pt 1):C1008C1017.
36.
Gravett MG, Witkin SS, Haluska GJ, Edwards JL, Cook MJ, Novy MJAn experimental model for intraamniotic infection and preterm labor in rhesus monkeys. Am J Obstet Gynecol. 1994;171(6):1660-1667.
37.
Hirsch E., Saotome I., Hirsh D.A model of intrauterine infection and preterm delivery in mice. Am J Obstet Gynecol. 1995;172(5):1598-1603.
38.
Kaga N., Katsuki Y., Obata M., Shibutani Y.Repeated administration of low-dose lipopolysaccharide induces preterm delivery in mice: a model for human preterm parturition and for assessment of the therapeutic ability of drugs against preterm delivery. Am J Obstet Gynecol . 1996;174(2):754-759.
