Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Journal of Basic and Clinical Physiology and Pharmacology

Editor-in-Chief: Horowitz, Michal

Editorial Board: Das, Kusal K. / Epstein, Yoram / S. Gershon MD, Elliot / Kodesh , Einat / Kohen, Ron / Lichtstein, David / Maloyan, Alina / Mechoulam, Raphael / Roth, Joachim / Schneider, Suzanne / Shohami, Esther / Sohmer, Haim / Yoshikawa, Toshikazu / Tam, Joseph


CiteScore 2016: 1.01

SCImago Journal Rank (SJR) 2016: 0.349
Source Normalized Impact per Paper (SNIP) 2016: 0.495

Online
ISSN
2191-0286
See all formats and pricing
More options …
Volume 28, Issue 3

Issues

The effect of extracellular ATP on rat uterine contraction from different gestational stages and its possible mechanisms of action

Hind A. Zafrah
  • Department of Physiology, College of Medicine, King Khalid University, Abha, Kingdom of Saudi Arabia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Mohammed F. Alotaibi
  • Corresponding author
  • Department of Physiology, College of Medicine, King Saud University, P.O. Box 2925, Riyadh 11461, Kingdom of Saudi Arabia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2017-03-30 | DOI: https://doi.org/10.1515/jbcpp-2016-0118

Abstract

Background:

The mechanisms underlying the onset of labor are not fully understood. Extracellular adenosine 5′-triphosphate (ATP) is known to cause uterine contractions in different species but the exact underlying mechanisms are poorly investigated to date. The aims of this study were to investigate the effect of extracellular ATP on spontaneous uterine contractions from different gestational stages and to elucidate its possible underlying mechanisms.

Methods:

Longitudinal uterine strips were obtained from rats in different gestational stages (nonpregnant, late-pregnant, and term-pregnant). The effects of 1 mM ATP were examined on uterine contractions generated spontaneously, depolarized by high-KCl (60 mM), induced by oxytocin (5 nM), in the presence of high external Ca2+, or in the absence of external Ca2+.

Results:

Application of 1 mM extracellular ATP significantly increased the force of spontaneous contraction in uterine strips obtained from all gestational stages with prominent increase in term-pregnant rats compared to other gestations. ATP significantly increased the force induced by depolarization (122%, p=0.010, n=6), oxytocin (129%, p=0.001, n=7), high-Ca2+ (145%, p=0.005, n=6) and it was able to cause transient contraction in the absence of external Ca2+ (33%, p<0.01).

Conclusions:

Extracellular ATP is able to increase the force and frequency of uterine contractions and its effect increases with the progression of pregnancy and it involves Ca2+ influx and release. These findings open a new window for clinicians to consider ATP as a therapeutic target to control the uterine activity during difficult labors.

Keywords: ATP; contraction; oxytocin; term-pregnant; uterus

References

  • 1.

    Young RC, Smith LH, McLaren MD. T-type and L-type calcium currents in freshly dispersed human uterine smooth muscle cells. Am J Obstet Gynecol 1993;169:785–92.Google Scholar

  • 2.

    North RA. Molecular physiology of P2X receptors. Physiol Rev 2002;82:1013–67.Google Scholar

  • 3.

    Miyoshi H, Yamaoka K, Garfield RE, Ohama K. Identification of a non-selective cation channel current in myometrial cells isolated from pregnant rats. Pflügers Archiv 2004;447: 457–64.Google Scholar

  • 4.

    Kimura T, Takemura M, Nomura S, Nobunaga T, Kubota Y, Inoue T, et al. Expression of oxytocin receptor in human pregnant myometrium. Endocrinology 1996;137:780–5.Google Scholar

  • 5.

    Olson DM. The role of prostaglandins in the initiation of parturition. Best Pract Res Clin Obstet Gynaecol 2003;17: 717–30.Google Scholar

  • 6.

    Hutchings G, Gevaert T, Deprest J, Nilius B, Williams O, De Ridder D. The effect of extracellular adenosine triphosphate on the spontaneous contractility of human myometrial strips. Eur J Obstet Gynecol Reprod Biol 2009;143:79–83.Google Scholar

  • 7.

    Takahara N, Ito S, Furuya K, Naruse K, Aso H, Kondo M, et al. Real-time Imaging of ATP release induced by mechanical stretch in human airway smooth muscle cells. Am J Respir Cell Mol Biol 2014;51:772–82.Google Scholar

  • 8.

    Hamada K, Takuwa N, Yokoyama K, Takuwa Y. Stretch activates Jun N-terminal kinase/stress-activated protein kinase in vascular smooth muscle cells through mechanisms involving autocrine ATP stimulation of purinoceptors. J Biol Chem 1998;273:6334–40.Google Scholar

  • 9.

    Buvinic S, Almarza G, Bustamante M, Casas M, López J, Riquelme M, et al. ATP released by electrical stimuli elicits calcium transients and gene expression in skeletal muscle. J Biol Chem 2009;284:34490–505.Google Scholar

  • 10.

    Tong YC, Hung YC, Shinozuka K, Kunitomo M, Cheng JT. Evidence of adenosine 5′-triphosphate release from nerve and P2X-purinoceptor mediated contraction during electrical stimulation of rat urinary bladder smooth muscle. J Urol 1997;158:1973–7.Google Scholar

  • 11.

    Todorov LD, Mihaylova-Todorova S, Craviso GL, Bjur R, Westfall D. Evidence for the differential release of the cotransmitters ATP and noradrenaline from sympathetic nerves of the guinea-pig vas deferens. J Physiol 1996;496:731.Google Scholar

  • 12.

    Dubyak GR, el-Moatassim C. Signal transduction via P2-purinergic receptors for extracellular ATP and other nucleotides. Am J Physiol Cell Physiol 1993;265:C577–606.Google Scholar

  • 13.

    Burnstock G. Purine and pyrimidine receptors. Cell Mol Life Sci 2007;64:1471–83.Google Scholar

  • 14.

    Burnstock G, Knight GE. Cellular distribution and functions of P2 receptor subtypes in different systems. Int Rev Cytol 2004;240:31–304.Google Scholar

  • 15.

    Bergner A, Sanderson MJ. ATP stimulates Ca2+ oscillations and contraction in airway smooth muscle cells of mouse lung slices. Am J Physiol Lung Cell Mol Physiol 2002;283:L1271–9.Google Scholar

  • 16.

    Lee H, Ro S, Keef K, Kim Y, Kim H, Horowitz B, et al. Differential expression of P2X‐purinoceptor subtypes in circular and longitudinal muscle of canine colon. Neurogastroenterol Motil 2005;17:575–84.Google Scholar

  • 17.

    Nagaoka M, Nara M, Tamada T, Kume H, Oguma T, Kikuchi T, et al. Regulation of adenosine 5′-triphosphate (ATP)-gated P2X 4 receptors on tracheal smooth muscle cells. Respir Physiol Neurobiol 2009;166:61–7.Google Scholar

  • 18.

    Piper AS, Hollingsworth M. P2‐purinoceptors mediating spasm of the isolated uterus of the non‐pregnant guinea‐pig. Br J Pharmacol 1996;117:1721–9.Google Scholar

  • 19.

    Suzuki Y. Contraction and prostaglandin biosynthesis by myometrium from non-pregnant and pregnant rabbits in response to adenosine 5′-triphosphate. Eur J Pharmacol 1991;195:93–9.Google Scholar

  • 20.

    Burnstock G, Holman M. Effect of drugs on smooth muscle. Annu Rev Pharmacol 1966;6:129–56.Google Scholar

  • 21.

    Sneddon P. Electrophysiology of autonomic neuromuscular transmission involving ATP. J Auton Nerv Syst 2000; 81:218–24.Google Scholar

  • 22.

    Ventura S, Dewalagama RK, Lau LC. Adenosine 5′‐triphosphate (ATP) is an excitatory cotransmitter with noradrenaline to the smooth muscle of the rat prostate gland. Br J Pharmacol 2003;138:1277–84.Google Scholar

  • 23.

    Ziganshin AU, Zaitzev AP, Zefirova JT, Ziganshina LE. P2 receptor-mediated responses in pregnant human uterus. Biomed Res 2003;14:171–3.Google Scholar

  • 24.

    McLaren G, Burke K, Buchanan K, Sneddon P, Kennedy C. Evidence that ATP acts at two sites to evoke contraction in the rat isolated tail artery. Br J Pharmacol 1998;124:5–12.Google Scholar

  • 25.

    Ziganshin AU, Zaitcev AP, Khasanov AA, Shamsutdinov AF, Burnstock G. Term-dependency of P2 receptor-mediated contractile responses of isolated human pregnant uterus. Eur J Obstet Gynecol Reprod Biol 2006;129:128–34.Google Scholar

  • 26.

    Vial C, Evans R. P2X receptor expression in mouse urinary bladder and the requirement of P2X1 receptors for functional P2X receptor responses in the mouse urinary bladder smooth muscle. Br J Pharmacol 2000;131:1489–95.Google Scholar

  • 27.

    Oguma T, Ito S, Kondo M, Makino Y, Shimokata K, Honjo H, et al. Roles of P2X receptors and Ca2+ sensitization in extracellular adenosine triphosphate‐induced hyperresponsiveness in airway smooth muscle. Clin Exp Allergy 2007;37:893–900.Google Scholar

  • 28.

    Lewis C, Evans R. Comparison of P2X receptors in rat mesenteric, basilar and septal (coronary) arteries. J Auton Nerv Syst 2000;81:69–74.Google Scholar

  • 29.

    Khanam T, Burnstock G. Changes in expression of P2X 1 receptors and connexin 43 in the rat myometrium during pregnancy. Fertil Steril 2007;88:1174–9.Google Scholar

  • 30.

    Kennedy C. ATP as a cotransmitter in the autonomic nervous system. Auton Neurosci 2015;191:2–15.Google Scholar

  • 31.

    Burnstock G. Release of vasoactive substances from endothelial cells by shear stress and purinergic mechanosensory transduction. J Anat 1999;194:335–42.Google Scholar

  • 32.

    Alehagen S, Wijma B, Lundberg U, Wijma K. Fear, pain and stress hormones during childbirth. J Psychosom Obstet Gynaecol 2005;26:153–65.Google Scholar

  • 33.

    Peebles D, Spencer J, Edwards A, Wyatt J, Reynolds E, Cope M, et al. Relation between frequency of uterine contractions and human fetal cerebral oxygen saturation studied during labour by near infrared spectroscopy. Br J Obstet Gynaecol 1994;101:44–8.Google Scholar

  • 34.

    Fuchs AR, Romero R, Keefe D, Parra M, Oyarzun E, Behnke E. Oxytocin secretion and human parturition: pulse frequency and duration increase during spontaneous labor in women. Am J Obstet Gynecol 1991;165:1515–23.Google Scholar

  • 35.

    Moore TR, Iams JD, Creasy RK, Burau KD, Davidson AL, Group UAiPW. Diurnal and gestational patterns of uterine activity in normal human pregnancy. Obstet Gynecol 1994;83:517–23.Google Scholar

  • 36.

    Main DM, Grisso JA, Wold T, Snyder ES, Holmes J, Chiu G. Extended longitudinal study of uterine activity among low-risk women. Am J Obstet Gynecol 1991;165:1317–22.Google Scholar

  • 37.

    Matthew A, Kupittayanant S, Burdyga T, Wray S. Characterization of contractile activity and intracellular Ca2+ signalling in mouse myometrium. J Soc Gynecol Investig 2004;11:207–12.Google Scholar

  • 38.

    Granger SE, Hollingsworth M, Weston A. Effects of calcium entry blockers on tension development and calcium influx in rat uterus. Br J Pharmacol 1986;87:147–56.Google Scholar

  • 39.

    Kupittayanant S, Burdyga T, Wray S. The effects of inhibiting Rho-associated kinase with Y-27632 on force and intracellular calcium in human myometrium. Pflügers Archiv 2001;443:112–14.Google Scholar

  • 40.

    Wibberley A, Chen Z, Hu E, Hieble JP, Westfall TD. Expression and functional role of Rho‐kinase in rat urinary bladder smooth muscle. Br J Pharmacol 2003;138:757–66.Google Scholar

  • 41.

    Buddhakala N, Talubmook C, Sriyotha P, Wray S, Kupittayanant S. Inhibitory effects of ginger oil on spontaneous and PGF2α-induced contraction of rat myometrium. Planta Med 2008;74:385–91.Google Scholar

  • 42.

    Inscho EW, Belott TP, Mason MJ, Smith JB, Navar LG. Extracellular ATP increases cytosolic calcium in cultured rat renal arterial smooth muscle cells. Clin Exp Pharmacol Physiol 1996;23:503–7.Google Scholar

  • 43.

    Christie A, Sharma V, Sheu S. Mechanism of extracellular ATP-induced increase of cytosolic Ca2+ concentration in isolated rat ventricular myocytes. J Physiol 1992;445:369.Google Scholar

  • 44.

    Shmigol A, Eisner D, Wray S. Simultaneous measurements of changes in sarcoplasmic reticulum and cytosolic [Ca2+] in rat uterine smooth muscle cells. J Physiol 2001;531:707–13.Google Scholar

  • 45.

    Batra S. Effect of oxytocin on calcium influx and efflux in the rat myometrium. Eur J Pharmacol 1986;120:57–61.Google Scholar

  • 46.

    Edman K, Schild H. The need for calcium in the contractile responses induced by acetylcholine and potassium in the rat uterus. J Physiol 1962;161:424.Google Scholar

  • 47.

    Bengtsson B, Chow E, Marshall J. Calcium dependency of pregnant rat myometrium: comparison of circular and longitudinal muscle. Biol Reprod 1984;30:869–78.Google Scholar

  • 48.

    Mounkaïla B, Marthan R, Roux E. Biphasic effect of extracellular ATP on human and rat airways is due to multiple P2 purinoceptor activation. Respir Res 2005;6:1.Google Scholar

  • 49.

    Alotaibi M, Arrowsmith S, Wray S. Hypoxia-induced force increase (HIFI) is a novel mechanism underlying the strengthening of labor contractions, produced by hypoxic stresses. Proc Natl Acad Sci USA 2015;112:9763–8.Google Scholar

About the article

Corresponding author: Mohammed F. Alotaibi, PhD, Department of Physiology, College of Medicine, King Saud University, P.O. Box 2925, Riyadh 11461, Kingdom of Saudi Arabia, Phone: +966 11 4672629, Fax: +966 11 4672567


Received: 2016-07-26

Accepted: 2017-02-09

Published Online: 2017-03-30

Published in Print: 2017-05-01


Author contributions: MA designed the research, HZ performed the experiments. MA and HZ analyzed the data. MA wrote the manuscript. MA and HZ revised and approved the final version. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: This study was funded by King Abdulaziz City for Science and Technology (KACST) (project number GSP-37-1123).

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Journal of Basic and Clinical Physiology and Pharmacology, Volume 28, Issue 3, Pages 209–217, ISSN (Online) 2191-0286, ISSN (Print) 0792-6855, DOI: https://doi.org/10.1515/jbcpp-2016-0118.

Export Citation

©2017 Walter de Gruyter GmbH, Berlin/Boston.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Craig P. Testrow, Arun V. Holden, Anatoly Shmygol, and Henggui Zhang
Scientific Reports, 2018, Volume 8, Number 1
[3]
Zorana Oreščanin-Dušić, Nikola Tatalović, Teodora Vidonja-Uzelac, Jelena Nestorov, Aleksandra Nikolić-Kokić, Ana Mijušković, Mihajlo Spasić, Roman Paškulin, Mara Bresjanac, and Duško Blagojević
Oxidative Medicine and Cellular Longevity, 2018, Volume 2018, Page 1
[4]
Geoffrey Burnstock
Frontiers in Pharmacology, 2017, Volume 8

Comments (0)

Please log in or register to comment.
Log in