Skip to main content

Advertisement

SpringerLink
Log in

MRP transporters as membrane machinery in the bradykinin-inducible export of ATP

  • ORIGINAL ARTICLE
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

Adenosine triphosphate (ATP) plays the role of an autocrine/paracrine signal molecule in a variety of cells. So far, however, the membrane machinery in the export of intracellular ATP remains poorly understood. Activation of B2-receptor with bradykinin-induced massive release of ATP from cultured taenia coli smooth muscle cells. The evoked release of ATP was unaffected by gap junction hemichannel blockers, such as 18α-glycyrrhetinic acid and Gap 26. Furthermore, the cystic fibrosis transmembrane regulator (CFTR) coupled Cl− channel blockers, CFTR(inh)172, 5-nitro-2-(3-phenylpropylamino)-benzoic acid, Gd3+ and glibenclamide, failed to suppress the export of ATP by bradykinin. On the other, the evoked release of ATP was greatly reduced by multidrug resistance protein (MRP) transporter inhibitors, MK-571, indomethacin, and benzbromarone. From western blotting analysis, blots of MRP 1 protein only, but not MRP 2 and MRP 3 protein, appeared at 190 kD. However, the MRP 1 protein expression was not enhanced after loading with 1 μM bradykinin for 5 min. Likewise, niflumic acid and fulfenamic acid, Ca2+-activated Cl− channel blockers, largely abated the evoked release of ATP. The possibility that the MRP transporter system couples with Ca2+-activated Cl− channel activities is discussed here. These findings suggest that MRP transporters, probably MRP 1, unlike CFTR-Cl− channels and gap junction hemichannels, may contribute as membrane machinery to the export of ATP induced by G-protein-coupled receptor stimulation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

ABC:

ATP-binding cassette

α-GA:

18-α-glycyrrhetinic acid

CFTR:

cystic fibrosis transmembrane regulator

CFTR(inh)172:

4-[[4-Oxo-2-thioxo-3-(3-trifluoromethyl)phenyl]-5-thiazo lidinylidene]methyl]benzoic acid

Gap 26:

Val-Cys-Tyr-Asp-Lys-Ser-Phe- Pro-Ile-Ser-His-Val-Arg

MK-571:

3-[[[3-[(1E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl] [[3-(dimethylamino)-3oxopropyl]thio]methyl]thio]propanoic acid

MRP:

multidrug resistance protein

NPPB:

5-nitro-2-(3-phenylpropylamino)-benzoic acid

SMCs:

smooth muscle cells

References

  • Abraham EH, Okunieff P, Scala S, Vos P, Oosterveld MJ, Chen AY, Shrivastav B (1997) Cystic fibrosis transmembrane conductance regulator and adenosine triphosphate. Science 275:1324–1326

    Article  PubMed  CAS  Google Scholar 

  • Braet K, Aspeslagh S, Vandamme W, Willecke K, Martin PEM, Evans WH, Leybaert L (2003a) Pharmacological sensitivity of ATP release triggered by photoliberation of inositol-1,4,5-trisphosphate and zero extracellular calcium in brain endothelial cells. J Cell Physiol 197:205–213

    Article  PubMed  CAS  Google Scholar 

  • Braet K, Vandamme W, Martin PEM, Evans WH, Leybaert L (2003b) Photoliberating inositol-1,4,5-trisphosphate triggers ATP release that is blocked by the connexin mimetic peptide gap 26. Cell Calcium 33:37–48

    Article  PubMed  CAS  Google Scholar 

  • Braunstein GM, Roman RM, Clancy JP, Kudlow BA, Taylor AL, Shylonsky VG, Jovov B, Peter K, Jilling T, Schwiebert EM (2001) Cystic fibrosis transmembrane conductance regulator facilitates ATP release by stimulating a separate ATP release channel for autocrine control of cell volume regulation. J Biol Chem 276:6621–6630

    Article  PubMed  CAS  Google Scholar 

  • Cantiello HF, Jackson GR Jr, Grosman CF, Prat AG, Borkan SC, Wang Y, Reisin IL, O’Riordan CR, Ausiello DA (1998) Electrodiffusional ATP movement through the cystic fibrosis transmembrane conductance regulator. Am J Physiol 274:C799–C809

    PubMed  CAS  Google Scholar 

  • Coco S, Calegari F, Pravettoni E, Pozzi D, Taverna E, Rosa P, Matteoli M, Verderio C (2003) Storage and release of ATP from astrocyte in culture. J Biol Chem 278:1354–1362

    Article  PubMed  CAS  Google Scholar 

  • Cotrina ML, Lin JHC, Alves-Rodrigues A, Liu S, Li J, Azmi-Ghadimi H, Kang J, Naus CCG, Nedergaard M (1998) Connexin regulate calcium signaling by controlling ATP release. Proc Natl Acad Sci USA 95:15735–15740

    Article  PubMed  CAS  Google Scholar 

  • Darby M, Kuzmiski JB, Panenka W, Feighan D, MacVicar BA (2003) ATP released from astrocytes during swelling activates chloride channels. J Neurophysiol 89:1870–1877

    Article  PubMed  CAS  Google Scholar 

  • Dutta AK, Sabirov LM, Uramoto H, Okada Y (2004) Role of ATP-conductive anion channel in ATP release from neonatal rat cardiomyocytes in ischemic or hypotonic conditions. J Physiol 559:799–812

    PubMed  CAS  Google Scholar 

  • Feranchak AP, Fitz JG, Roman RM (2000) Volume-sensitive purinergic signaling in human hepatocytes. J Hepatol 33:174–182

    Article  PubMed  CAS  Google Scholar 

  • Grygorczyk R, Hanrahan JW (1997) CFTR-independent ATP release from epithelial cells triggered by mechanical stimuli. Am J Physiol 272:C1058–C1066

    PubMed  CAS  Google Scholar 

  • Hazama A, Shimizu T, Ando-Akatsuka Y, Hayashi S, Tanaka S, Maeno E, Okada Y (1999) Swelling-induced, CFTR-independent ATP release from a human epithelial cell line—lack of correlation with volume-sensitive Cl− channels. J Gen Physiol 114:525–533

    Article  PubMed  CAS  Google Scholar 

  • Hooijberg JH, Jansen G, Assaraf YG, Kathmann I, Pieters R, Laan AC, Veeman AJP, Kaspers GJL, Peters GJ (2004) Folate concentration dependent transport actibity of the multidrug resistance protein 1 (ABCC1). Biochem Pharmacol 67:1541–1548

    Article  PubMed  CAS  Google Scholar 

  • Ji Y, Morris ME (2005) Transport of dietary phenethyl isothiocyanate is mediated by multidrug resistance protein 2 but not P-glycoprotein. Biochem Pharmacol 70:640–647

    Article  PubMed  CAS  Google Scholar 

  • Katsuragi T, Matsuo K, Sato C, Sato Y, Honda K, Kamiya H, Furukawa T (1996) Non-neuronal release ATP and inositol 1, 4, 5-trisphosphate accumulation evoked by P2- and M-receptor stimulation in guinea pig ileal segments. J Pharmacol Exp Ther 277:747–752

    PubMed  CAS  Google Scholar 

  • Katsuragi T, Sato C, Lou G, Honda K (2002) Inositol(1,4,5)trisphosphate signal triggers a receptor-mediated ATP release. Biochem Biophys Res Commun 293:686–690

    Article  PubMed  CAS  Google Scholar 

  • Katsuragi T, Sato C, Usune S, Ueno S, Segawa M, Migita K (2008) Caffeine-inducible ATP release is mediated by Ca2+-signal transducing system from the endoplasmic leticulum to mitochondria. Naunyn-Schmiedeb Arch Pharmacol 378:93–101

    Article  CAS  Google Scholar 

  • Lader AS, Xiao Y-F, O’Riordan CR, Prat AG, Jackson GR Jr, Cantiello HF (2000) C-AMP activates an ATP-permeable pathway in neonatal rat cardiac myocytes. Am J Physiol 27(9):C173–C187

    Google Scholar 

  • Linsdell P, Hanrahan JW (1999) Substrates of multidrug resistance-associated proteins block the cystic fibrosis transmembrane conductance regulator chloride channel. Br J Pharmacol 126:1471–1477

    Article  PubMed  CAS  Google Scholar 

  • Matsuo K, Katsuragi T, Fujiki S, Sato C (1997) ATP release and contraction mediated by different P2-receptor subtypes in guinea-pig ileal smooth muscle. Br J Pharmacol 121:1744–1748

    Article  PubMed  CAS  Google Scholar 

  • Migita K, Lu L, Zhao Y, Honda K, Iwamoto T, Kita S, Katsuragi T (2005) Adenosine induces ATP release via an inositol 1,4,5-trisphosphate signaling pathway in MDCK cells. Biochem Biophys Res Commun 328:1211–1215

    Article  PubMed  CAS  Google Scholar 

  • Migita K, Zhao Y, Katsuragi T (2007) Mitochondria play an important role in adenosine-induced ATP release from Madin-Darby canine kidney cells. Biochem Phamacol 73:1676–1682

    Article  CAS  Google Scholar 

  • Mitchell CH (2001) Release of ATP by a human retinal pigment epithelial cell line: potential for autocrine stimulation through subretinal space. J Physiol 534:193–202

    Article  PubMed  CAS  Google Scholar 

  • Pearson RA, Dale N, Liaudet E, Mobbs P (2005) ATP released via gap junction hemichannels from the pigment epithelium regulates neural retinal progenitor proliferation. Neuron 46:731–744

    Article  PubMed  CAS  Google Scholar 

  • Prime-Chapman HM, Fearn RA, Cooper AE, Moore V, Hirst BH (2004) Differential multidrug resistance-associated protein 1 through 6 isoform expression and function in human intestinal epithelial caco-2 cells. J Pharmacol Exp Ther 311:476–484

    Article  PubMed  CAS  Google Scholar 

  • Queiroz G, Geibicke-Haerter PJ, Schobert A, Starke K, von Kügelgen I (1997) Release of ATP from cultured rat astrocytes elicited by glutamate receptor activation. Neuroscience 78:1203–1208

    Article  PubMed  CAS  Google Scholar 

  • Ralevic V, Burnstock G (1998) Receptors for purines and pyrimidines. Pharmacol Rev 50:413–492

    PubMed  CAS  Google Scholar 

  • Reddy MM, Quinton PM, Haws C, Wine JJ, Grygorczyk R, Tabcharani JA, Hanrahan JW, Gunderson KL, Kopito RR (1996) Failure of the cystic fibrosis transmembrane conductance regulator to conduct ATP. Science 271:1876–1879

    Article  PubMed  CAS  Google Scholar 

  • Reisin IL, Prat AG, Abraham EH, Amara JF, Gregory RJ, Ausiello DA, Cantiello HF (1994) The cystic fibrosis transmembrane conductance regulator is a dual ATP and chloride channel. J Biol Chem 269:20584–20591

    PubMed  CAS  Google Scholar 

  • Roman RM, Fitz JG (1999) Emerging roles of purinergic signaling in gastrointestinal epithelial secretion and hepatobiliary function. Gastroenterology 116:964–979

    Article  PubMed  CAS  Google Scholar 

  • Roman RM, Lomri N, Braunstein G, Feranchak AP, Simeoni LA, Davison AK, Mechetner E, Schwiebert EM, Fitz JG (2001) Evidence for multidrug resistance-1 P-glycoprotein-dependent regulation of cellular ATP permeability. J Membr Biol 183:165–173

    Article  PubMed  CAS  Google Scholar 

  • Sauer H, Stanelle R, Hescheler J, Wartenberg M (2002) The DC electrical-field-induced Ca2+ response and growth stimulation of multicellular tumor spheroids are mediated by ATP release and purinergic receptor stimulation. J Cell Sci 115:3265–3273

    PubMed  CAS  Google Scholar 

  • Schlosser SF, Burgstahler AD, Nathanson MH (1996) Isolated rat hepatocytes can signal to other hepatocytes and bile duct cells by release of nucleotides. Proc Natl Acad Sci USA 93:9948–9953

    Article  PubMed  CAS  Google Scholar 

  • Sprague RS, Ellsworth ML, Stephenson AH, Lonigro AJ (2001) Participation of cAMP in a signal-transduction pathway relating erythrocyte deformation to ATP release. Am J Physiol 281:C1158–C1164

    CAS  Google Scholar 

  • Stout CE, Constantin JL, Naus CCG, Charles AC (2002) Intercellular calcium signaling in astrocytes via ATP release through connexin hemichannels. J Biol Chem 277:10482–10488

    Article  PubMed  CAS  Google Scholar 

  • Tamesue S, Sato C, Katsuragi T (1998) ATP release caused by bradykinin, substance P and histamine from intact and cultured smooth muscles of guinea pig vas deferens. Naunyn-Schmiedeb Arch Pharmacol 357:240–244

    Article  CAS  Google Scholar 

  • Walsh DE, Harvey BJ, Urbach V (2000) CFTR regulation of intracellular calcium in normal and cystic fibrosis human airway epithelia. J Membr Biol 177:209–219

    Article  PubMed  CAS  Google Scholar 

  • Watt WC, Lazarowski ER, Boucher RC (1998) Cystic fibrosis transmembrane regulator-independent release of ATP. Its implications for the regulations of P2Y2 receptors in airway epithelia. J Biol Chem 273:14053–14058

    Article  PubMed  CAS  Google Scholar 

  • Zhao Y, Migita K, Sato C, Usune S, Iwamoto T, Katsuragi T (2007) Endoplasmic reticulum is a key organelle in bradykinin-triggered ATP release from cultured smooth muscle cells. J Pharm Sci 105:57–65

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by Grant-in Aid for Scientific Research (17590234) From the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by the Uehara Memorial Foundation.

Author information

Authors and Affiliations

  1. Medical Research Center, School of Medicine, Fukuoka University, Fukuoka, 814-0180, Japan

    Jing Sun & Takeshi Katsuragi

  2. Department of Pediatric Dentistry, School of Dentistry of Shanghai Tongi University, Shanghai, 200072, People’s Republic of China

    Yumei Zhao

  3. Rehabilitation Medicine, Institute Brain Science, Horosaki University School of Medicine, Aomori, 036-8562, Japan

    Keisuke Migita

  4. Department of Dental Implantology, School of Stomatology, Tongji University, Shanghai, 200072, People’s Republic of China

    Jing Sun

Authors
  1. Yumei Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Keisuke Migita
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jing Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takeshi Katsuragi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Takeshi Katsuragi.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Supplemental data 1

Fluorescence scopic (a, stained with α-actin) and phase contrast scopic b pictures were taken from the same cultured cells. (PPT 327 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhao, Y., Migita, K., Sun, J. et al. MRP transporters as membrane machinery in the bradykinin-inducible export of ATP. Naunyn-Schmied Arch Pharmacol 381, 315–320 (2010). https://doi.org/10.1007/s00210-009-0490-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-009-0490-0

Keywords

Search

Navigation