Skip to main content
PMC home page
Journal of Cellular and Molecular Medicine logoLink to Journal of Cellular and Molecular Medicine
. 2007 May 1;10(3):734–748. doi: 10.1111/j.1582-4934.2006.tb00433.x

Angiotensin II-induced delayed stimulation of phospholipase C γ1 requires activation of both phosphatidiylinositol 3-kinase γ and tyrosine kinase in vascular myocytes

Lala Rakotoarisoa 1,#, Valérie Carricaburu 1,#, Catherine Leblanc 1, Chantal Mironneau 1, Jean Mironneau 1, Nathalie Macrez 1
PMCID: PMC3933155  PMID: 16989733

Abstract

In vascular smooth muscles, angiotensin II (AII) has been reported to activate phospholipase C (PLC) and phosphatidylinositol 3-kinase (PI3K). We investigated the time-dependent effects of AII on both phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) and inositol phosphates (InsPs) accumulation in permeabilized microsomes from rat portal vein smooth muscle in comparison with those of noradrenaline (NA). AII stimulated an early production of PtdInsP3 (within 30 s) followed by a delayed production of InsPs (within 3-5 min), in contrast to NA which activated only a fast production of InsPs. The use of pharmacological inhibitors and antibodies raised against the PI3K and PLC isoforms expressed in portal vein smooth muscle showed that AII specifically activated PI3Kδ and that this isoform was involved in the AII-induced stimulation of InsPs accumulation. NA-induced InsPs accumulation depended on PLCβ1 activation whereas AII-induced InsPs accumulation depended on PLCγ1 activation. AII-induced PLCδ1 activation required both tyrosine kinase and PI3Kδ since genistein and tyrphostin B48 (inhibitors of tyrosine kinase), LY294002 and wortmannin (inhibitors of PI3K) and anti-PI3Kδ antibody abolished AII-induced stimulation of InsPs accumulation. Increased tyrosine phosphorylation of PLCβ1 was only detected for long-lasting applications of AII and was suppressed by genistein. These data indicate that activation of both PI3Kβ and tyrosine kinase is a prerequisite for AII-induced stimulation of PLCβ1 in vascular smooth muscle and suggest that the sequential activation of the three enzymes may be responsible for the slow and long-lasting contraction induced by AII.

Keywords: angiotensin II, phospholipase C gamma, phosphatidylinositol 3-kinase gamma, tyrosine-kinase, smooth muscle cells

References

  • 1.Mironneau J, Mironneau C, Grosset A, Hamon G, Savineau JP. Action of angiotensin II on the electrical and mechanical activity of rat uterine smooth muscle. Eur J Pharmacol. 1980;68:275–85. doi: 10.1016/0014-2999(80)90525-7. [DOI] [PubMed] [Google Scholar]
  • 2.Hamon G, Worcel M. Mechanism of action of angiotensin II on excitation-contraction coupling in the rat portal vein. Br J Pharmacol. 1982;75:425–32. doi: 10.1111/j.1476-5381.1982.tb09157.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Pelet C, Mironneau C, Rakotoarisoa L, Neuilly G. Angiotensin II receptor subtypes and contractile responses in portal vein smooth muscle. Eur J Pharmacol. 1995;279:15–24. doi: 10.1016/0014-2999(95)00125-5. [DOI] [PubMed] [Google Scholar]
  • 4.Griendling KK, Tsuda T, Berk BC, Alexander RW. Angiotensin II stimulation of vascular smooth musclecells. Secondary signalling mechanisms. Am J Hypertens. 1989;2:659–65. doi: 10.1093/ajh/2.8.659. [DOI] [PubMed] [Google Scholar]
  • 5.Rhee SG, Bae YS. Regulation of phosphoinositides-specific phospholipase C isozymes. J Biol Chem. 1997;272:15045–8. doi: 10.1074/jbc.272.24.15045. [DOI] [PubMed] [Google Scholar]
  • 6.Marrero MB, Paxton WG, Duff JL, Berk BC, Bernstein KE. Angiotensin II stimulates tyrosine phosphorylation of phospholipase C-γ1 in vascular smooth muscle cells. J Biol Chem. 1994;269:10935–9. [PubMed] [Google Scholar]
  • 7.Venema RC, Ju H, Venema VJ, Schieffer B, Harp JB, Ling BN, Eaton DC, Marrero MB. Angiotensin II-induced association of phospholipase Cγ1 with the G-protein coupled AT1 receptor. J Biol Chem. 1998;273:7703–8. doi: 10.1074/jbc.273.13.7703. [DOI] [PubMed] [Google Scholar]
  • 8.Bae YS, Cantley LG, Chen CS, Kim SR, Kwon KS, Rhee SG. Activation of phospholipase C-γ by phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem. 1998;273:4465–9. doi: 10.1074/jbc.273.8.4465. [DOI] [PubMed] [Google Scholar]
  • 9.Falasca M, Logan SK, Lehto VP, Baccante G, Lemmon MA, Schelessinger J. Activation of phospholipase Cγ by PI 3-kinase-induced PH domain-mediated membrane targeting. EMBO J. 1998;17:414–22. doi: 10.1093/emboj/17.2.414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Rameh LE, Rhee SG, Spokes K, Kazlauskas A, Cantley LC, Cantley LG. Phosphoinosisitde 3-kinase regulates phospholipase Cγ-mediated calcium signalling. J Biol Chem. 1998;273:23750–7. doi: 10.1074/jbc.273.37.23750. [DOI] [PubMed] [Google Scholar]
  • 11.Macrez N, Mironneau C, Carricaburu V, Quignard JF, Babich A, Czupalla C, Nurnberg B, Mironneau J. Phosphoinositide 3-kinase isoforms selectively couple receptors to vascular L-type Ca2+ channels. Circ Res. 2001;89:692–9. doi: 10.1161/hh2001.097864. [DOI] [PubMed] [Google Scholar]
  • 12.Quignard JF, Mironneau J, Carricaburu V, Fournier B, Babich A, Nurnberg B, Mironneau C, Macrez N. Phosphoinositide 3-kinase γ mediates angiotensin IIinduced stimulation of L-type calcium channels in vascular myocytes. J Biol Chem. 2001;276:32545–51. doi: 10.1074/jbc.M102582200. [DOI] [PubMed] [Google Scholar]
  • 13.Macrez-Lepretre N, Kalkbrenner F, Morel JL, Schultz G, Mironneau J. G protein heterotrimer Gα13β1γ3 couples the angiotensin AT1A receptor to increase in cytoplasmic Ca2+ in rat portal vein myocytes. J Biol Chem. 1997;272:10095–102. doi: 10.1074/jbc.272.15.10095. [DOI] [PubMed] [Google Scholar]
  • 14.Viard P, Exner T, Maier U, Mironneau J, Nurnberg B, Macrez N. Gβγ dimers stimulate vascular L-type Ca2+ channels via phosphoinositide 3-kinase. FASEB J. 1999;13:685–94. doi: 10.1096/fasebj.13.6.685. [DOI] [PubMed] [Google Scholar]
  • 15.Morel JL, Marcrez-Lepretre N, Mironneau J. Angiotensin II-activated Ca2+ from intracellular stores in rat portal vein myocytes. Br J Pharmacol. 1996;118:73–8. doi: 10.1111/j.1476-5381.1996.tb15368.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Arnaudeau S, Macrez-Lepretre N, Mironneau J. Activationof calcium sparks by angiotensin II in vascular myocytes. Biochem Biophys Res Commun. 1996;222:809–15. doi: 10.1006/bbrc.1996.0808. [DOI] [PubMed] [Google Scholar]
  • 17.Bradford MM. A rapid and sensitive method for the quantitation of microgram of protein quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1996;72:248–54. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  • 18.Claro E, Picatoste F, Fain JN. Agonist stimulation of phosphoinositide breakdown in brain membranes. Meth Neurosci. 1993;18:38–47. [Google Scholar]
  • 19.Treyer M, Walde P, Oberholzer T. Permeability enhancement of lipid vesicles to nucleotides by use of sodium cholate: basic studies and aplication to an enzymecatalyzed reaction occuring inside the vesicles. Langmuir. 2002;18:1043–50. [Google Scholar]
  • 20.Viard P, Macrez N, Mironneau C, Mironneau J. Involvement of both G protein αs and βγ subunits in β-adrenergic stimulation of vascular L-type Ca2+ channels. Br J Pharmacol. 2001;132:669–76. doi: 10.1038/sj.bjp.0703864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Carricaburu V, Fournier B. Phosphoinositide fatty acids regulate phosphatidylinositol 5-kinase, phospholipase C and protein kinase C activities. Eur J Biochem. 2001;268:1238–49. doi: 10.1046/j.1432-1327.2001.01984.x. [DOI] [PubMed] [Google Scholar]
  • 22.Vidulescu C, Mironneau J, Mironneau C, Popescu LM. Phospholipases C and A2 trigger and sustain contraction, while phospholipase D intermediates relaxation in noradrenaline-stimulated portal vein smooth muscle. J Med Biochem. 2000;4:22–31. [Google Scholar]
  • 23.Nakanishi S, Kakita S, Takahashi I, Kawahara K, Tsukuda E, Sano T, Yamada K, Yoshida M, Kase H, Matsuda Y, Hashimoto Y, Nonomura Y. Wortmannin, a microbial product inhibitor of myosin light chain kinase. J Biol Chem. 1992;267:2157–63. [PubMed] [Google Scholar]
  • 24.Macrez-Leprêtre N, Morel JL, Mironneau J. Effects of phospholipase C inhibitors on Ca2+ channel stimulation and Ca2+ release from intracellular stores evoked by α1Aand α2A-adrenoceptors in rat portal vein myocytes. Biochem Biophys Res Commun. 1996;218:30–4. doi: 10.1006/bbrc.1996.0006. [DOI] [PubMed] [Google Scholar]
  • 25.Quignard JF, Rakotoarisoa L, Mironneau J, Mironneau C. Stimulation of L-type Ca2+ channels by inositol pentakis- and hexakisphosphates in rat vascular smooth muscle cells. J Physiol. 2003;549:729–37. doi: 10.1113/jphysiol.2002.037473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Saward L, Zahradka P. Angiotensin II activates phosphatidylinositol 3-kinase in vascular smooth muscle cells. Circ Res. 1997;81:249–57. doi: 10.1161/01.res.81.2.249. [DOI] [PubMed] [Google Scholar]
  • 27.Touyz R, Schiffrin E. Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells. Pharmacol Rev. 2000;52:639–72. [PubMed] [Google Scholar]
  • 28.Homma Y, Sakamoto H, Tsunoda M, Aoki M, Takenawa T, Ooyama T. Evidence for involvement of phospholipase C-γ2 in signal transduction of platelet- derived growth factor in vascular smooth muscle cells. Biochem J. 1993;290:649–53. doi: 10.1042/bj2900649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.La Belle EF, Polyak F. Phospholipase C β2 in vascular smooth muscle. J Cell Physiol. 1996;169:358–63. doi: 10.1002/(SICI)1097-4652(199611)169:2<358::AID-JCP15>3.0.CO;2-5. [DOI] [PubMed] [Google Scholar]
  • 30.Blayney L, Gapper P, Rix C. Identification of phospholipase C β isoforms and their location in cultured vascular smooth muscle cells of pig, human and rat. Cardiovasc Res. 1998;40:564–72. doi: 10.1016/s0008-6363(98)00193-x. [DOI] [PubMed] [Google Scholar]
  • 31.Schelling JR, Nkemere N, Konieczkowski M, Martin KA, Dubyak GR. Angiotensin II activates the β1 isoform of phospholipase C in vascular smooth muscle cells. Am J Physiol Cell Physiol. 1997;272:C1558–66. doi: 10.1152/ajpcell.1997.272.5.C1558. [DOI] [PubMed] [Google Scholar]
  • 32.Ushio-Fukaï M, Griendling KK, Akers M, Lyons PR, Alexander RW. Temporal dispersion of activation of phospholipase C-β1 and -γ isoforms by angiotensin II in vascular smooth muscle cells. Role of αq/11, α12 and βγ G protein subunits. J Biol Chem. 1998;273:19772–7. doi: 10.1074/jbc.273.31.19772. [DOI] [PubMed] [Google Scholar]
  • 33.Macrez-Lepretre N, Kalkbrenner F, Schultz G, Mironneau J. Distinct functions of Gq and G11 in coupling α1-adrenoceptors to Ca2+ release and Ca2+ entry in rat portal vein myocytes. J Biol Chem. 1997;272:5261–8. doi: 10.1074/jbc.272.8.5261. [DOI] [PubMed] [Google Scholar]
  • 34.Lee CH, Park D, Wu D, Rhee SG, Simon MI. Members of the Gq alpha subunit gene family activate phospholipase C beta isozymes. J Biol Chem. 1992;267:16044–7. [PubMed] [Google Scholar]
  • 35.Ishida M, Marrero MB, Schieffer B, Ishida T, Bernstein KE, Berk BC. Angiotensin II activates pp60c- Src in vascular smooth muscle cells. Circ Res. 1995;77:1053–9. doi: 10.1161/01.res.77.6.1053. [DOI] [PubMed] [Google Scholar]
  • 36.Touyz RM, Wu XH, He G, Park GB, Chen X, Vacher J, Rajapurohitam V, Schiffrin EL. Role of c-Src in the regulation of vascular contraction and Ca2+ signaling by angiotensin II in human vascular smooth muscle cells. J Hypertens. 2001;19:441–9. doi: 10.1097/00004872-200103000-00012. [DOI] [PubMed] [Google Scholar]
  • 37.Haendeler J, Yin G, Hojo Y, Saito Y, Melaragno M, Yan C, Sharma VK, Heller M, Aebersold R, Berk BC. GIT1 mediates Src-depdndent activation of phospholipae Cγ angiotensin II andepidermal growth factor. J Biol Chem. 2003;278:499–44. doi: 10.1074/jbc.M307317200. [DOI] [PubMed] [Google Scholar]
  • 38.Sekiya F, Bae YS, Rhee SG. Regulation of phospholipase C isozymes: activation of phospholipase C-γ in the absence of tyrosine-phosphorylation. Chem Phys Lipids. 1999;98:3–11. doi: 10.1016/s0009-3084(99)00013-4. [DOI] [PubMed] [Google Scholar]
  • 39.Vidulescu C, Mironneau J, Mironneau C, Popescu LM. Messenger molecules of the phospholipase signaling system have dual effects on vascular smooth muscle contraction. J Cell Mol Med. 2000;4:196–206. doi: 10.1111/j.1582-4934.2000.tb00117.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Lepretre N, Mironneau J, Arnaudeau S, Tanfin Z, Harbon S, Guilon G, Ibarrondo J. Activation of alpha-1a adrenoceptors mobilizes calcium from the intracellular stores in myocytes from rat portal vein. J. Pharm. Exp. Therap. 1994;268:167–74. [PubMed] [Google Scholar]
  • 41.Le Blanc C, Mironneau C, Barbot C, Henaff M, Bondeva T, Wetzker R, Macrez N. Regulation ofvascular L-type Ca2+ channels by phosphatidylinositol 3,4,5-trisphosphate. Circ Res. 2004;95:300–7. doi: 10.1161/01.RES.0000138017.76125.8b. [DOI] [PubMed] [Google Scholar]
  • 42.Patterson RL, Van Rossum DB, Ford DL, Hurt KJ, Bae SS, Suh PG, Kurosaki T, Snyder SH, Gill DL. Phospholipase C-γ is required for agonist-induced Ca2+ entry. Cell. 2002;111:529–41. doi: 10.1016/s0092-8674(02)01045-0. [DOI] [PubMed] [Google Scholar]
  • 43.Van Rossum DB, Patterson RL, Sharma S, Barrow RK, Kornberg M, Gill DL, Snyder SH. Phospholipase Cγ1 controls surface expression of TRPC3 through an intermolecular PH domain. Nature. 2005;434:99–104. doi: 10.1038/nature03340. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Cellular and Molecular Medicine are provided here courtesy of Blackwell Publishing

RESOURCES