Pertussis toxin inhibits the angiotensin II and serotonin‐induced rise of free cytoplasmic calcium in cultured smooth muscle cells from rat aorta

Berthou, Christian; Marmé, Dieter

doi:10.1016/0014-5793(87)81552-1

Cited by 33 publications

(7 citation statements)

References 25 publications

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“…The complete blockade of the AII‐induced [Ca 2+ ] i rise by PTX indicates that AII raises [Ca 2+ ] i in human VSMCs via a PTX‐sensitive heterotrimeric G protein. Previous studies have concluded that G proteins are involved in [Ca 2+ ] i elevation in response to this agent in smooth muscle, but have yielded no consensus regarding PTX sensitivity (Bruns & Marme, 1987; Dostal et al , 1990; Ohya & Sperelakis, 1991). The failure of lovastatin to affect responses to AII and LDL is surprising.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of lovastatin on mitogen induced calcium influx in human cultured vascular smooth muscle cells

Clunn

Lymn

Schächter

et al. 1997

British J Pharmacology

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1 In this study the e ect of lovastatin, an inhibitor of cholesterol and isoprenoid synthesis, on the rises in intracellular calcium concentration ([Ca 2+ ] i ) induced by platelet derived growth factor BB (PDGF-BB), angiotensin II (AII), low density lipoproteins (LDL) and foetal calf serum (FCS) was examined in human cultured vascular smooth muscle cells (VSMC) from saphenous vein. Changes in [Ca 2+ ] i were measured in cell suspensions by the Ca 2+ sensitive probe, fura 2. 2 Incubation with lovastatin for 24 ± 26 h markedly reduced the peak rise and sustained phase of [Ca 2+ ] i elevation in response to PDGF-BB but the responses to AII, LDL and FCS were una ected. Further experiments showed that lovastatin pretreatment inhibited PDGF-BB induced Ca 2+ in¯ux but not intracellular Ca 2+ release. This inhibition could be overcome by co-incubation with mevalonic acid. 3 Pretreatment of cells with the heterotrimeric G protein inhibitor pertussis toxin for up to 24 h completely abolished AII-induced [Ca 2+ ] i rises but the response to PDGF-BB was una ected. 4 The tyrosine kinase inhibitor genistein largely abolished PDGF-BB-induced [Ca 2+ ] i elevation but had no signi®cant e ect on AII-induced responses. 5 Pre-incubation with lovastatin had no e ect on the level of tyrosine phosphorylation of PDGF-b receptors (as measured by Western blot) in response to the PDGF-BB ligand. 6 PDGF-BB elicits Ca 2+ in¯ux via a tyrosine kinase-dependent mechanism distinct from the heterotrimeric G protein coupled pathway utilized by AII. Lovastatin most likely acts by inhibition of isoprenylation (via blockade of isoprenoid synthesis) of an intermediate molecule involved in PDGF-BBinduced Ca 2+ in¯ux.

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Section: Discussionmentioning

confidence: 99%

Differential effects of lovastatin on mitogen induced calcium influx in human cultured vascular smooth muscle cells

Clunn

Lymn

Schächter

et al. 1997

British J Pharmacology

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“…The existence of a GTP-sensitive pool in VSMC is shown by the ability of GTP[S] and NaF to stimulate inositol phosphate accumulation in a dose-dependent manner. Previous reports had suggested that hormonal signalling in VSMC was mediated by a G-protein based on observations that GTP analogues altered the affinity of the receptor for angiotensin II [43], and that pertussis toxin inhibited Ca2" mobilization in angiotensin II [17] or noradrenaline [18]-stimulated cells. In contrast with the latter reports, no sensitivity of angiotensin II-induced IP3 formation to pertussis toxin was observed here, although the concentration of pertussis toxin used in our study was sufficient to modify all of the available substrate (Fig.…”

Section: Discussionmentioning

confidence: 99%

Cholera toxin modulation of angiotensin II-stimulated inositol phosphate production in cultured vascular smooth muscle cells

Socorro

Alexander

Griendling

1990

Biochemical Journal

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Activation of phospholipase C by angiotensin II in vascular smooth muscle has been postulated to be mediated by an unidentified GTP-binding protein (G-protein). Using a permeabilized preparation of myo-[3H]inositol-labelled cultured vascular smooth muscle cells, we examined the ability of a non-hydrolysable analogue of GTP, guanosine 5'-[gamma-thio]triphosphate (GTP[S]), to stimulate inositol phosphate formation. GTP[S] (5 min exposure) stimulated inositol polyphosphate release by up to 3.8-fold in a dose-dependent manner, with an EC50 (concn. producing half-maximal stimulation) of approx. 50 microM. Inositol bisphosphate (IP2) and inositol trisphosphate (IP3) accumulations were also stimulated by NaF (5-20 mM). Furthermore, angiotensin II-induced inositol phosphate formation could be potentiated by a submaximal concentration of GTP[S] (10 microM), and this treatment appeared to interfere with the normal termination mechanism of the initial hormonal signal. The G-protein mediating angiotensin II-stimulated phospholipase C activation was insensitive to pertussis toxin at an exposure time and concentration which were sufficient to completely ADP-ribosylate all available substrate (100 ng/ml, 16 h). In contrast, a similar incubation with cholera toxin markedly inhibited angiotensin II-stimulated IP2 and IP3 release by 67 +/- 6% and 62 +/- 6% respectively. Cholera toxin appeared to inhibit angiotensin II stimulation of phospholipase C by a dual mechanism: it caused a 45% decrease in angiotensin II receptor number, and also inhibited G-protein transduction as assessed by GTP[S]-stimulated IP2 formation. This latter inhibition may be secondary to an increase in cyclic AMP, since it could be simulated by addition of dibutyryl cyclic AMP. Thus angiotensin II-stimulated inositol phosphate formation is cholera-toxin-sensitive, and is mediated by a pertussis-toxin-insensitive G-protein, which may be involved directly in termination of early signal generation.

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“…The cellular action of AII in vascular tissue is initiated by hormone binding to cell surface receptors. This hormone-receptor complex, possibly in association with a specific guanine nucleotide-binding protein (1,2), activates a phospholipase in the plasma membrane (3). The subsequent hydrolysis of phosphatidyl inositol bisphosphate and phosphatidyl inositol results in the activation of inositol trisphosphate and diacylglycerol intracellular signals (4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Role of receptor cycling in the regulation of angiotensin II surface receptor number and angiotensin II uptake in rat vascular smooth muscle cells.

Ullian¹,

Linas²

1989

J. Clin. Invest.

126

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In vivo data on the factors controlling angiotensin II (AII) cell surface binding are conflicting. We studied the specific effects of All on All binding in rat mesenteric artery vascular smooth muscle cells in culture. Incubation with unlabeled AII at 21°C resulted in time-and concentration-dependent decreases in All surface binding at 4°C, with a 30% reduction after exposure to 300 nM AII for 15 min. Reductions in cell surface binding were due to decrements in receptor number rather than changes in binding affinity. Loss of surface receptors was mediated by receptor internalization as maneuvers that blocked ligand internalization (cold temperature and phenylarsine oxide [PAOI) attenuated AII-induced loss of surface receptors. After removal of AII, recovery of surface binding was rapid (t1/2 = 15 min) and was mediated by reinsertion of a preexisting pool of receptors into the surface membrane rather than by new receptor synthesis. To determine the role of receptor cycling on AII-induced surface receptor loss, cells were incubated with the endosomal inhibitor chloroquine during exposure to AII at 21°C. Incubation with All plus chloroquine resulted in a 70% greater loss of surface binding than after incubation with AII alone. To determine the role of receptor cycling on uptake of ligand, cells were incubated with PAO or endosomal inhibitors during exposure to AII at 4 and 21°C. Compared with buffer these agents did not alter All uptake at 40C, but decreased uptake by 12-50% at 21°C. These results indicate that after binding All receptors cycle and that receptor cycling attenuates All-induced losses of surface receptors and enhances ligand uptake by providing a continuous source of receptors to the cell surface.

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Pertussis toxin inhibits the angiotensin II and serotonin‐induced rise of free cytoplasmic calcium in cultured smooth muscle cells from rat aorta

Cited by 33 publications

References 25 publications

Differential effects of lovastatin on mitogen induced calcium influx in human cultured vascular smooth muscle cells

Differential effects of lovastatin on mitogen induced calcium influx in human cultured vascular smooth muscle cells

Cholera toxin modulation of angiotensin II-stimulated inositol phosphate production in cultured vascular smooth muscle cells

Role of receptor cycling in the regulation of angiotensin II surface receptor number and angiotensin II uptake in rat vascular smooth muscle cells.

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