Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin II (ANG II) and arginine vasopressin (AVP) act on area postrema (AP) neurons to modulate the baroreflex. Because activation of AP neurons by either ANG II or AVP increases intracellular free Ca2+ concentrations ([Ca2+]i), the goal of this study was to analyze the factors affecting the [Ca2+]i responses to ANG II and AVP. Neurons were recovered from 14- to 16-day old rats and studied after 8-14 days in culture by use of the microscopic digital image analysis for fura 2-loaded cells. The effects of ANG II (100 nM) and AVP (100 nM) on [Ca2+]i were determined in normal (2 mM) and low (< 10 nM) extracellular Ca2+ concentrations. In 143 of 240 neurons, ANG II increased [Ca2+]i 4.65-fold after 20 s, and a similar response was observed in the absence of extracellular Ca2+ (3.65-fold after 20 s). After 60 s of observation, steady-state levels of increased [Ca2+]i were still present under both conditions. Pretreatment with AT1 antagonist or pertussis toxin abolished the response to ANG II. AVP also increased [Ca2+]i (3.6-fold at peak, 20 s) in normal and low extracellular Ca2+. Pretreatment with AVP V1 antagonist or pertussis toxin abolished the response to AVP. This study indicates that ANG II-induced increases in [Ca2+]i are independent of extracellular Ca2+ concentrations and involve the activation of AT1 receptors and a pertussis toxin-sensitive G protein. Although AVP affects a fewer number of AP neurons, the mechanisms of activation are also independent of extracellular Ca2+ concentration and are mediated by a pertussis toxin-sensitive G protein.
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PMID:Subcellular mechanisms of angiotensin II and arginine vasopressin activation of area postrema neurons. 876 Feb 1

Angiotensin II (ANG II), a potent growth-promoting factor of vascular smooth muscle cells (VSMC), induces activation of mitogen-activated protein (MAP) kinases and subsequent expression of the c-fos protooncogene in VSMC. However, it remains obscure whether ANG II induces activation of the ras protooncogene product (Ras), and if it does, whether Ras is involved in signaling from the ANG II receptor to the MAP kinase pathway in VSMC. In cultured VSMC, ANG II activated Ras comparably to epidermal growth factor. ANG II-induced Ras activation was detectable within 1 min and maximal at 2-5 min. The ANG II type 1 (AT1) receptor antagonist, CV-11974, completely inhibited this reaction. Pertussis toxin treatment of VSMC inhibited ANG II-induced Ras activation by approximately 70% but had no effect on ANG II-induced MAP kinase activation and c-fos expression. These results indicate that ANG II activates Ras via AT1 receptors, which are predominantly linked to a G protein of the Gi subfamily in VSMC1 and suggest that Ras activation may not be a prerequisite for ANG II-induced MAP kinase activation and c-fos expression in this cell type.
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PMID:Angiotensin II type 1 receptor-mediated activation of Ras in cultured rat vascular smooth muscle cells. 877 Jan 1

Angiotensin II (ANG II) is the most potent and the most physiologically important stimulator of aldosterone synthesis and secretion from the adrenal zona glomerulosa. Because steroidogenesis by adrenal glomerulosa (AG) cells is mediated in part by Ca2+ influx through T- and L-type Ca2+ channels, we evaluated whether T-type Ca2+ channels are regulated by ANG II. We observe that ANG II enhances T-type Ca2+ current by shifting the voltage dependence of channel activation to more negative potentials. This shift is transduced by the ANG II type 1 receptor. The effect of the hormone is not mediated by Ca2+/calmodulin-dependent protein kinase II (CaMKII) as it is not prevented by CaMKII(281-302), a peptide inhibitor of the catalytic region of the kinase. Rather, this shift is mediated by the activation of a G protein, Gi, because it is abolished by cell pretreatment with pertussis toxin and by cell dialysis with a monoclonal antibody generated against recombinant Gi alpha. This effect of ANG II on T-type Ca2+ channels should increase Ca2+ entry in AG cells at physiologically relevant voltages and result in a sustained increase in aldosterone secretion.
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PMID:Angiotensin II stimulates T-type Ca2+ channel currents via activation of a G protein, Gi. 889 41

1. Angiotensin II (AII) and the endothelins (ET) are known to be potent trophic stimuli in various cells including cardiomyocytes. In order to characterize further these effects we studied, in neonatal rat ventricular cardiomyocytes, the effects of several endothelin-receptor antagonists and the AT1-receptor antagonist losartan on AII- and endothelin-induced inositol phosphate (IP)-formation (assessed as accumulation of total [3H]-IPs in myo-[3H]-inositol prelabelled cells) and increase in rate of protein synthesis (assessed as [3H]-phenylalanine incorporation). 2. Endothelin (10 pM-1 microM) concentration-dependently increased IP-formation (max. increase at 100 nM ET-1: 130 +/- 14% above basal, n = 25) and [3H]-phenylalanine incorporation (max. increase at 1 microM: 52 +/- 4% above basal, n = 16) with an order of potency: ET-1 > > ET-3. Both effects were antagonized by the ETA/ETB-receptor antagonist bosentan and the ETA-receptor antagonist BQ-123, but not affected by the ETB-receptor antagonist IRL 1038 and the AT1-receptor antagonist losartan. 3. Pretreatment of the cells with 500 ng ml-1 pertussis toxin (PTX) overnight that completely inactivated PTX-sensitive G-proteins did not attenuate but rather enhance ET-1-induced IP-formation. On the other hand, in PTX-pretreated cardiomyocytes ET-1-induced [3H]-phenylalanine incorporation was decreased by 39 +/- 5% (n = 5). 4. All (1 nM-1 microM) concentration-dependently increased IP-formation (max. increase at 1 microM: 42 +/- 7% above basal, n = 16) and [3H]-phenylalanine incorporation (max. increase at 1 microM: 29 +/- 2%, n = 9). These effects were antagonized by losartan, but they were also antagonized by bosentan and BQ-123. 5. In well-defined cultures of cardiomyocytes (not contaminated with non-myocyte cells) All failed to increase [3H]-phenylalanine incorporation: addition of non-myocyte cells to the cardiomyocytes restored All-induced increase in [3H]-phenylalanine incorporation. 6. We conclude that, in rat neonatal ventricular cardiomyocytes, (a) the ET-1-induced increase in rate of protein synthesis (through ETA-receptor stimulation) involves at least two signalling pathways: one via a PTX-insensitive G-protein coupled to IP-formation, and the other one via a PTX-sensitive G-protein, and (b) the trophic effects of All are brought about via local ET-1 secretion upon AT1-receptor stimulation in neonatal rat ventricular non-myocyte cells.
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PMID:Trophic effect of angiotensin II in neonatal rat cardiomyocytes: role of endothelin-1 and non-myocyte cells. 914 95

1. Angiotensin II had a bimodal effect on human neutrophil migration. Low concentrations of angiotensin II stimulated random migration. At a concentration of 10(-10) M it caused a maximal increase of migration; migration increased from 47.2 +/- 2.1 microns in the absence of angiotensin II, to 73.1 +/- 2.2 microns with 10(-10) M angiotensin II present in the lower compartment of the Boyden chamber (n = 5, P < 0.001). Stimulation of migration by angiotensin II was partly chemotactic and partly chemokinetic. Angiotensin II concentrations of 10(-8) M and higher inhibited chemotactic peptide-stimulated chemotaxis. 2. The stimulant effect of angiotensin II on migration was completely dependent on extracellular Ca2+. In the presence of 1 mM Ca2+, angiotensin II stimulated migration to 76.1 +/- 1.7 microns, while migration in the absence of Ca2+ was 42.2 +/- 1.9 microns (n = 4, P < 0.001). Different types of calcium channel blockers either moderately or strongly inhibited angiotensin II-activated migration. Stimulation of migration by angiotensin II in intact cells required higher concentrations of Ca2+ than in electroporated cells. This supports the view that there is an influx of Ca2+ through the plasma membrane, and a requirement of calcium for an intracellular target. 3. Angiotensin II-stimulated migration was inhibited by pertussis toxin; from 71.6 +/- 2.0 microns in the absence, to 43.6 +/- 1.5 microns in the presence of pertussis toxin (n = 4, P < 0.001). Migration of electroporated neutrophils stimulated by angiotensin II was synergistically enhanced by GTP gamma S. This suggests that one or more G-proteins are involved in the activating effect of angiotensin II. 4. Inhibitors of soluble guanylate cyclase and antagonists of cyclic GMP-dependent kinase strongly inhibited the activating effect of angiotensin II. The results suggest that the activating effect of angiotensin II is mediated by cyclic GMP and by cyclic GMP-dependent kinase.
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PMID:The stimulation of human neutrophil migration by angiotensin IL: its dependence on Ca2+ and the involvement of cyclic GMP. 920 29

The proliferation and hypertrophy of renal tubular cells are primary features in the progression of both acute and chronic renal disease often indicating a poor prognosis. Angiotensin II (ANG II), acting alone or in combination with other growth factors, has been implicated in this process. The aims of this study were to identify the importance of both ANG II and serum-derived factors upon cellular DNA synthesis and protein synthesis in renal proximal tubular cells and to identify the roles of the ANG II receptor subtypes in these processes together with the underlying intracellular signalling mechanisms involved. Primary cultures of renal proximal tubular cells were prepared from freshly isolated rat kidney cortex. Cells were cultured in either serum-replete Dulbecco's modified Eagle's/Ham's F12 or serum-deplete defined medium containing insulin, hydrocortisone, sodium selenite, transferrin, and tri-iodothyronine. Cells were incubated with ANG II (10(-10), 10(-8), 10(-6) M) for 24-120 h either alone or in combination with losartan, PD123319, or pertussis toxin. Incubation of proximal tubular cells in the presence of serum and ANG II (10(-8) M) induced a significant early (24 h) increase in DNA synthesis, together with a significant late (96 h) increase in protein content. [3H]thymidine uptake increased by 56% (p < 0.001) and total protein content by 23% (p < 0.05). In defined media, ANG II (10(-8) M) stimulated protein synthesis only. [3H]uridine uptake, [3H]leucine uptake, and total protein content increased by 25, 57, and 17% (p < 0.05), respectively. In both serum-replete and serum-deplete media, the effects upon protein synthesis of ANG II were inhibited by pertussis toxin and losartan, but not by PD123319. ANG II is clearly a potent stimulator of renal tubular cell DNA and protein synthesis-a response mediated via the AT1 receptor coupled to a pertussis toxin sensitive Gi protein.
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PMID:Selective antagonism of the AT1 receptor inhibits the effect of angiotensin II on DNA and protein synthesis of rat proximal tubular cells. 920 86

Angiotensin II type 2 (AT2) receptors are involved in the inhibition of cell proliferation as well as in apoptosis and neuronal differentiation, through intracellular signalling pathways that remain poorly defined. The present study examines the effect of AT2-receptor stimulation on growth-factor-induced pathways leading to the activation of mitogen-activated protein (MAP) kinases. In N1E-115 neuroblastoma cells, AT2 receptors inhibit the activity of MAP kinases induced by serum as well as by epidermal growth factor. The inhibitory effect of angiotensin II (Ang II) is rapid and transient, and affects both ERK1 and ERK2 (extracellular signal-related protein kinase) isoforms of the enzyme. AT2-mediated MAP kinase inactivation is not sensitive to pertussis toxin or okadaic acid, but involves a vanadate-sensitive protein tyrosine phosphatase (PTP). Expression of MAP kinase phosphatase-1 (MKP-1) is not significantly modified upon AT2-receptor activation, and insensitivity to actinomycin D also rules out transcriptional induction of other MKPs as a possible mechanism for AT2-mediated inactivation of MAP kinases. In addition, we report here that both in N1E-115 cells and in Chinese hamster ovary cells expressing recombinant human AT2 receptors, Ang II rapidly stimulates the catalytic activity of SHP-1, a soluble PTP that has been implicated in termination of signalling by cytokine and growth-factor receptors. These findings thus demonstrate functional negative cross-talk between heptahelical AT2 receptors and receptor tyrosine kinases, and suggest that SHP-1 tyrosine phosphatase is an early transducer of the AT2 receptor signalling pathway.
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PMID:Angiotensin II type 2 receptors mediate inhibition of mitogen-activated protein kinase cascade and functional activation of SHP-1 tyrosine phosphatase. 923 Jan 27

Cellular processes leading to renal tubular hypertrophy may contribute to the development of progressive renal disease. Angiotensin II (ANG II) is a prime agent that has been linked to the progression of renal disease by a host of mechanisms, including the induction of tubular epithelial hypertrophy and stimulation of extracellular matrix biosynthesis. All components of a functional renin-angiotensin system reside within the renal tubule. Epithelial cells exhibit distinct patterns of growth behavior after stimulation with ANG II (namely, hypertrophy of proximal tubule segments and proliferation of more distal segments). The hypertrophic action of ANG II is mediated through high-affinity AT1-receptors, involves activation of pertussis-toxin sensitive G1 proteins, and depends on a decrease in intracellular cAMP. In addition, ANG II induces sequential activation of MAP kinases and S6 kinase, and leads to activation of early immediate genes and the modulation of a series of cyclins and cyclin-dependent kinases. There is also compelling evidence that the ANG II-induced epithelial hypertrophy and the stimulated-synthesis of collagen type IV are mediated by increased transcription and production of TGF-beta. ANG II-mediated inhibition of protein degradation may further increase protein content. The hypertrophic response to ANG II is greater in medium with high glucose concentration. Blockade of the action of ANG II prevents the renal hypertrophy and the tubulointerstitial fibrosis in animal models of chronic renal diseases (independent of changes in systemic or glomerular hemodynamics), in part through interception of ANG II-mediated induction of TGF-beta expression.
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PMID:Renal tubular hypertrophy induced by angiotensin II. 931 13

Angiotensin II (ANG II) has long been known for its pressor and growth-promoting effects, which are both mediated by the AT1 receptor. By contrast, the AT2 receptor has recently been reported to mediate inhibition of proliferation through as yet undefined mechanisms. We report here that in bovine adrenal fasciculata cells ANG II by itself does not affect growth but inhibits basic fibroblast growth factor (bFGF)-induced DNA synthesis and blocks the cells in G1 phase. Consistent with this, ANG II inhibits cyclin D1 expression and cyclin D1-associated kinase activity. The antimitogenic effect of ANG II is partly mimicked by the AT2-selective agonist CGP-42112. It is also blocked partly and in an additive fashion by the AT1- and AT2-selective antagonists losartan and PD-123319, indicating the contribution of both receptor subtypes to this response. AT1-dependent antiproliferation is selectively blocked by the cyclooxygenase inhibitor indomethacin and restored by prostaglandin E2, whereas AT2-receptor-mediated inhibition of growth is suppressed by the tyrosine phosphatase inhibitors orthovanadate and bpV(pic). Both pathways are, however, pertussis toxin sensitive. We hypothesize that, in fasciculata cells, the AT1 receptor inhibits bFGF-induced proliferation by stimulating prostaglandin synthesis, whereas the AT2 receptor mediates its effect through a pathway that requires protein tyrosine phosphatase activation.
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PMID:ANG II AT1 and AT2 receptors both inhibit bFGF-induced proliferation of bovine adrenocortical cells. 935 77

Angiotensin II (Ang II) elicits an Ang II type 2 (AT2) receptor-mediated increase in delayed-rectifier K+ current (IK) in neurons cultured from newborn rat hypothalamus and brainstem. This effect involves a pertussis toxin (PTX)-sensitive Gi protein and is abolished by inhibition of serine and threonine phosphatase 2A (PP-2A). Here, we determined that Ang II stimulates [3H]arachidonic acid (AA) release from cultured neurons via AT2 receptors. This effect of Ang II was blocked by inhibition of phospholipase A2 (PLA2) and by PTX. Because AA and its metabolites are powerful modulators of neuronal K+ currents, we investigated the involvement of PLA2 and AA in the AT2 receptor-mediated stimulation of IK by Ang II. Single-cell reverse transcriptase (RT)-PCR analyses revealed the presence of PLA2 mRNA in neurons that responded to Ang II with an increase in IK. The stimulation of neuronal IK by Ang II was attenuated by selective inhibitors of PLA2 and was mimicked by application of AA to neurons. Inhibition of lipoxygenase (LO) enzymes significantly reduced both Ang II- and AA-stimulated IK, and the 12-LO metabolite of AA 12S-hydroxyeicosatetraenoic acid (12S-HETE) stimulated IK. These data indicate the involvement of a PLA2, AA, and LO metabolite intracellular pathway in the AT2 receptor-mediated stimulation of neuronal IK by Ang II. Furthermore, the demonstration that inhibition of PP-2A abolished the stimulatory effects of Ang II, AA, and 12S-HETE on neuronal IK but did not alter Ang II-stimulated [3H]-AA release suggests that PP-2A is a distal event in this pathway.
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PMID:Angiotensin II type 2 receptor stimulation of neuronal delayed-rectifier potassium current involves phospholipase A2 and arachidonic acid. 942 10


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