Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2010

Open Access 01-12-2010 | Primary research

Bradykinin increases resensitization of purinergic receptor signaling in glioma cells

Authors: Héctor E López-Valdés, Luis Beltran-Parrazal, Kevin C Brennan, Andrew C Charles

Published in: Cancer Cell International | Issue 1/2010

Login to get access

Abstract

Background

Purinergic receptor-mediated signaling plays an important role in the function of glial cells, including glial tumor cells. Bradykinin is also an important paracrine mediator which is highly expressed in brain tumors and may correlate with their pathological grade. Interaction between bradykinin and purinergic signaling may therefore be involved in the regulation of glial tumor cells.

Results

We examined the effect of bradykinin on glial purinergic signaling in an immortalized glioma cell line. Confocal calcium imaging revealed that ATP evokes an increase in [Ca2+]i in the U87 human astrocytoma cell line. This response was reduced with repetitive application of ATP, likely due to receptor desensitization. However exposure to bradykinin increased the Ca2+ response to a second application of ATP, consistent with increased resensitization. The bradykinin effect on resensitization was similar in the absence of extracellular Ca2+ or in the presence of the PKC activator PMA, but was inhibited by the protein phosphatase inhibitor okadaic acid and the PI3K inhibitor LY294002.

Conclusions

Modulation of protein phosphatases and the PI3K pathway may represent a mechanism by which bradykinin potentiates purinergic signaling in glial cells.
Appendix
Available only for authorised users
Literature
1.
James G, Butt AM: P2Y and P2X purinoceptor mediated Ca2+ signalling in glial cell pathology in the central nervous system. Eur J Pharmacol. 2002, 447: 247-260. 10.1016/S0014-2999(02)01756-9.CrossRefPubMed
2.
Burnstock G: Physiology and Pathology of Purinergic Neurotransmission. Physiol Rev. 2007, 87: 659-797. 10.1152/physrev.00043.2006.CrossRefPubMed
3.
Charles AC, Merrill JE, Dirksen ER, Sanderson MJ: Intercellular signaling in glial cells: calcium waves and oscillations in response to mechanical stimulation and glutamate. Neuron. 1991, 6: 983-992. 10.1016/0896-6273(91)90238-U.CrossRefPubMed
4.
Guthrie PB, Knappenberger J, Segal M, Bennett MV, Charles AC, Kater SB: ATP released from astrocytes mediates glial calcium waves. J Neurosci. 1999, 19: 520-528.PubMed
5.
Stout CE, Constantin JL, Naus CC, Charles AC: Intercellular calcium signaling in astrocytes via ATP release through connexin hemichannels. J Biol Chem. 2002, 277: 10482-10488. 10.1074/jbc.M109902200.CrossRefPubMed
6.
Basarsky TA, Duffy SN, Andrew RD, MacVicar BA: Imaging spreading depression and associated intracellular calcium waves in brain slices. J Neurosc. 1998, 18: 7189-7199.
7.
Chuquet J, Hollender L, Nimchinsky EA: High-resolution in vivo imaging of the neurovascular unit during spreading depression. J Neurosci. 2007, 27: 4036-4044. 10.1523/JNEUROSCI.0721-07.2007.CrossRefPubMed
8.
Fam SR, Gallagher CJ, Salter MW: P2Y(1) purinoceptor-mediated Ca(2+) signaling and Ca(2+) wave propagation in dorsal spinal cord astrocytes. J Neurosci. 2000, 20: 2800-2808.PubMed
9.
Newman EA: Propagation of intercellular calcium waves in retinal astrocytes and Müller cells. J Neurosci. 2001, 21: 2215-2223.PubMedCentralPubMed
10.
Peters O, Schipke CG, Hashimoto Y, Kettenmann H: Different mechanisms promote astrocyte Ca2+ waves and spreading depression in the mouse neocortex. J Neurosci. 2003, 23: 9888-9896.PubMed
11.
Charles A: Intercellular calcium waves in glia. Glia. 1998, 24: 39-49. 10.1002/(SICI)1098-1136(199809)24:1<39::AID-GLIA5>3.0.CO;2-W.CrossRefPubMed
12.
Fiacco TA, McCarthy KD: Astrocyte calcium elevations: properties, propagation, and effects on brain signaling. Glia. 2006, 54: 676-90. 10.1002/glia.20396.CrossRefPubMed
13.
14.
Morrone FB, Oliveira DL, Gamermann P, Stella J, Wofchuk S, Wink MR, Meurer L, Edelweiss MI, Lenz G, Battastini AM: In vivo glioblastoma growth is reduced by apyrase activity in a rat glioma model. BMC Cancer. 2006, 6: 226-10.1186/1471-2407-6-226.PubMedCentralCrossRefPubMed
15.
White N, Burnstock G: P2 receptors and cancer. Trends Pharmacol Sci. 2006, 27: 211-217. 10.1016/j.tips.2006.02.004.CrossRefPubMed
16.
Drake MT, Shenoy SK, Lefkowitz RJ: Trafficking of G protein-coupled receptors. Circ Res. 2006, 99: 570-582. 10.1161/01.RES.0000242563.47507.ce.CrossRefPubMed
17.
Ferguson SS: Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling. Pharmacol Rev. 2001, 53: 1-24.PubMed
18.
Ferguson SS, Caron MG: G protein-coupled receptor adaptation mechanisms. Semin Cell Dev Biol. 1998, 9: 119-127. 10.1006/scdb.1997.0216.CrossRefPubMed
19.
Moreau ME, Garbacki N, Molinaro G, Brown NJ, Marceau F, Adam A: The kallikrein-kinin system: current and future pharmacological targets. J Pharmacol Sci. 2005, 99: 6-38. 10.1254/jphs.SRJ05001X.CrossRefPubMed
20.
Hsieh HL, Yen MH, Jou MJ, Yang CM: Intracellular signaling underlying bradykinin-induced matrix metalloproteinase-9 expression in rat brain astrocyte-1. Cell Signal. 2004, 16: 1163-1176. 10.1016/j.cellsig.2004.03.021.CrossRefPubMed
21.
Leeb-Lundberg LM, Marceau F, Müller-Esterl W, Pettibone DJ, Zuraw BL: International union of pharmacology. XLV. Classification of the kinin receptor family: from molecular mechanisms to pathophysiological consequences. Pharmacol Rev. 2005, 57: 27-77. 10.1124/pr.57.1.2.CrossRefPubMed
22.
Cholewinski AJ, Stevens G, McDermott AM, Wilkin GP: Identification of B2 bradykinin binding sites on cultured cortical astrocytes. J Neurochem. 1991, 57: 1456-1458. 10.1111/j.1471-4159.1991.tb08314.x.CrossRefPubMed
23.
Burch RM, Axelrod J: Dissociation of bradykinin-induced prostaglandin formation from phosphatidylinositol turnover in Swiss 3T3 fibroblasts: evidence for G protein regulation of phospholipase A2. Proc Natl Acad Sci USA. 1987, 84: 6374-6378. 10.1073/pnas.84.18.6374.PubMedCentralCrossRefPubMed
24.
Stephens GJ, Cholewinski AJ, Wilkin GP, Djamgoz MB: Calcium-mobilizing and electrophysiological effects of bradykinin on cortical astrocyte subtypes in culture. Glia. 1993, 9: 269-279. 10.1002/glia.440090405.CrossRefPubMed
25.
Yanaga F, Hirata M, Koga T: Evidence for coupling of bradykinin receptors to a guanine-nucleotide binding protein to stimulate arachidonate liberation in the osteoblast-like cell line, MC3T3-E1. Biochim Biophys Acta. 1991, 1094: 139-146. 10.1016/0167-4889(91)90001-E.CrossRefPubMed
26.
Raidoo DM, Sawant S, Mahabeer R, Bhoola KD: Kinin receptors are expressed in human astrocytic tumor cells. Immunopharmacology. 1999, 43: 255-263. 10.1016/S0162-3109(99)00097-1.CrossRefPubMed
27.
Graness A, Adomeit A, Heinze R, Wetzker R, Liebmann C: A novel mitogenic signaling pathway of bradykinin in the human colon carcinoma cell line SW-480 involves sequential activation of a Gq/11 protein, phosphatidylinositol 3-kinase beta, and protein kinase C epsilon. J Biol Chem. 1998, 273: 32016-32022. 10.1074/jbc.273.48.32016.CrossRefPubMed
28.
Wang YB, Peng C, Liu YH: Low dose of bradykinin selectively increases intracellular calcium in glioma cells. J Neurol Sci. 2007, 258: 44-51. 10.1016/j.jns.2007.02.031.CrossRefPubMed
29.
Zhao Y, Xue Y, Liu Y, Fu W, Jiang N, An P, Wang P, Yang Z, Wang Y: Study of correlation between expression of bradykinin B2 receptor and pathological grade in human gliomas. Br J Neurosurg. 2005, 19: 322-326. 10.1080/02688690500305555.CrossRefPubMed
30.
Paukert M, Hidayat S, Grunder S: The P2X(7) receptor from Xenopus laevis: formation of a large pore in Xenopus oocytes. FEBS Lett. 2002, 513: 253-258. 10.1016/S0014-5793(02)02324-4.CrossRefPubMed
31.
Czubayko U, Reiser G: Desensitization of P2U receptor in neuronal cell line. Different control by the agonists ATP and UTP, as demonstrated by single-cell Ca2+ responses. Biochem J. 1996, 320: 215-219.PubMedCentralCrossRefPubMed
32.
Verderio C, Matteoli M: ATP mediates calcium signaling between astrocytes and microglial cells: modulation by IFN-gamma. J Immunol. 2001, 166: 6383-6391.CrossRefPubMed
33.
Beltran-Parrazal L, López-Valdés HE, Brennan KC, Díaz-Muñoz M, de Vellis J, Charles AC: Mitochondrial transport in processes of cortical neurons is independent of intracellular calcium. Am J Physiol Cell Physiol. 2006, 291: C1193-1197. 10.1152/ajpcell.00230.2006.CrossRefPubMed
34.
Otero M, Garrad RC, Velazquez B, Hernandez-Perez MG, Camden JM, Erb L, Clarke LL, Turner JT, Weisman GA, Gonzalez FA: Mechanisms of agonist-dependent and -independent desensitization of a recombinant P2Y2 nucleotide receptor. Mol Cell Biochem. 2000, 205: 115-123. 10.1023/A:1007018001735.CrossRefPubMed
35.
Santiago-Perez LI, Flores RV, Santos-Berrios C, Chorna NE, Krugh B, Garrad RC, Erb L, Weisman GA, Gonzalez FA: P2Y(2) nucleotide receptor signaling in human monocytic cells: activation, desensitization and coupling to mitogen-activated protein kinases. J Cell Physiol. 2001, 187: 196-208. 10.1002/jcp.1063.CrossRefPubMed
36.
Flores RV, Hernández-Pérez MG, Aquino E, Garrad RC, Weisman GA, Gonzalez FA: Agonist-induced phosphorylation and desensitization of the P2Y2 nucleotide receptor. Mol Cell Biochem. 2005, 280: 35-45. 10.1007/s11010-005-8050-5.PubMedCentralCrossRefPubMed
37.
Weick M, Wiedemann P, Reichenbach A, Bringmann A: Resensitization of P2Y receptors by growth factor-mediated activation of the phosphatidylinositol-3 kinase in retinal glial cells. Invest Ophthalmol Vis Sci. 2005, 46: 1525-1532. 10.1167/iovs.04-0417.CrossRefPubMed
38.
Bony C, Roche S, Shuichi U, Sasaki T, Crackower MA, Penninger J, Mano H, Puceat M: A specific role of phosphatidylinoitol 3-kinase gamma. A regulation of autonomic Ca(2)+ oscillations in cardiac cells. J Cell Biol. 2001, 152: 717-728. 10.1083/jcb.152.4.717.PubMedCentralCrossRefPubMed
39.
Maier R, Glatz A, Mosbacher J, Bilbe G: Cloning of P2Y6 cDNAs and Identification of a Pseudogene: Comparison of Receptor Subtype Expression in Bone and Brain Tissues. Biochem Biophys Res Commun. 1997, 237: 297-302. 10.1006/bbrc.1997.7135.CrossRefPubMed
40.
Tulapurkar ME, Zundorf G, Reiser G: Internalization and desensitization of a green fluorescent protein-tagged P2Y nucleotide receptor are differently controlled by inhibition of calmodulin-dependent protein kinase II. J Neurochem. 2006, 96: 624-634. 10.1111/j.1471-4159.2005.03594.x.CrossRefPubMed
41.
Morrone FB, Jacques-Silva MC, Horn AP, Bernardi A, Schwartsmann G, Rodnight R, Lenz G: Extracellular nucleotides and nucleosides induce proliferation and increase nucleoside transport in human glioma cell lines. J Neurooncol. 2003, 64: 211-218. 10.1023/A:1025699932270.CrossRefPubMed
42.
Neary JT: Trophic actions of extracellular ATP: gene expression profiling by DNA array analysis. J Auton Nerv Syst. 2000, 81: 200-204. 10.1016/S0165-1838(00)00154-5.CrossRefPubMed
43.
Neary JT, Kang Y, Bu Y, Yu E, Akong K, Peters CM: Mitogenic signaling by ATP/P2Y purinergic receptors in astrocytes: involvement of a calcium-independent protein kinase C, extracellular signal-regulated protein kinase pathway distinct from the phosphatidylinositol-specific phospholipase C/calcium pathway. J Neurosci. 1999, 19: 4211-4220.PubMed
44.
Borlongan CV, Emerich DF: Facilitation of drug entry into the CNS via transient permeation of blood brain barrier: laboratory and preliminary clinical evidence from bradykinin receptor agonist, Cereport. Brain Res Bull. 2003, 60: 297-306. 10.1016/S0361-9230(03)00043-1.CrossRefPubMed
45.
Simard M, Arcuino G, Takano T, Liu QS, Nedergaard M: Signaling at the gliovascular interface. J Neurosci. 2003, 23: 9254-9262.PubMed
46.
Raidoo DM, Bhoola KD: Pathophysiology of the kallikrein-kinin system in mammalian nervous tissue. Pharmacol Ther. 2006, 79: 105-127. 10.1016/S0163-7258(98)00011-4.CrossRef
47.
Franke H, Krugel U, Illes P: P2 receptors and neuronal injury. Pflugers Arch. 2006, 452: 622-644. 10.1007/s00424-006-0071-8.CrossRefPubMed
48.
Millan MJ: The induction of pain: an integrative review. Prog Neurobiol. 1999, 57: 1-164. 10.1016/S0301-0082(98)00048-3.CrossRefPubMed
49.
Abbracchio MP, Burnstock G, Boeynaems JM, Barnard EA, Boyer JL, Kennedy C, Knight GE, Fumagalli M, Gachet C, Jacobson KA, Weisman GA: International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy. Pharmacol Rev. 2006, 58: 281-341. 10.1124/pr.58.3.3.PubMedCentralCrossRefPubMed
Metadata
Title
Bradykinin increases resensitization of purinergic receptor signaling in glioma cells
Authors
Héctor E López-Valdés
Luis Beltran-Parrazal
Kevin C Brennan
Andrew C Charles
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2010
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-10-35

Other articles of this Issue 1/2010

Cancer Cell International 1/2010 Go to the issue

Erratum

Erratum to: Targeting the angiotensin II type 2 receptor (AT2R) in colorectal liver metastases

Review

Novel molecular imaging platform for monitoring oncological kinases

Editorial

Reflections on the responsible conduct of cancer research

Primary research

Lowering the apoptotic threshold in colorectal cancer cells by targeting mitochondria

Primary research

ASPM-associated stem cell proliferation is involved in malignant progression of gliomas and constitutes an attractive therapeutic target

Primary research

Determination of the differentiation capacities of murines' primary mononucleated cells and MC3T3-E1 cells
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits