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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of an intracellular Ca2+ depletor (ryanodine), a Ca2+ channel antagonist (felodipine), a protein kinase C inhibitor (staurosporine) as well as caffeine, cholera and pertussis toxin have been examined on noradrenaline-induced contractions in aortic rings from rats pretreated i.v. with either saline or phenoxybenzamine for 7 days. Ryanodine (3 and 10 microM) was able to both potentiate and inhibit noradrenaline-evoked contractions in aortic rings from phenoxybenzamine-treated rats. However, ryanodine did not affect the concentration-response curves to noradrenaline in tissues from saline-treated rats. Further, felodipine (1 and 10 nM) and staurosporine (10 nM) inhibited noradrenaline-induced contractions in aortic rings from phenoxybenzamine- but not saline-treated rats. Pertussis toxin (100 ng/ml) also inhibited contractions produced by noradrenaline in rings from phenoxybenzamine- but not saline-treated rats. In contrast to these observations, both caffeine (1 mM) and cholera toxin (3 micrograms/ml) inhibited noradrenaline-evoked contractions in aortic rings from phenoxybenzamine- and saline-treated rats. The results suggest that chronic receptor blockade by phenoxybenzamine leads to alteration in alpha-adrenoceptor-mediated signal transduction in the aorta. The changes include alteration in Ca2+ handling at the plasmalemmal and intracellular levels, as well as an altered action of pertussis toxin-sensitive G-protein, but not of cholera toxin-sensitive G-protein.
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PMID:Effects of chronic receptor blockade on excitation-contraction coupling in rat aortic rings. 798 55

1. We have examined the inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) responses in bovine aortic endothelial (BAE) cells to purines (ATP, ADP and analogues) and the pyrimidine, uridine triphosphate (UTP). 2. Exchange of medium on BAE cells in the absence of agonist was found to be a stimulus for Ins(1,4,5)P3 generation. BAE cells stimulated with 100 microM ATP, 30 microM 2MeSATP (an agonist at P2Y-purinoceptors but not nucleotide receptors) or 100 microM UTP (an agonist at nucleotide receptors but not P2Y-purinoceptors) gave Ins(1,4,5)P3 responses above that caused by exchange of medium. The time course was rapid, with peak response within the first 5 s and levels returning close to basal after 30 s of stimulation. 3. Significant differences in Ins(1,4,5)P3 responses to 100 microM UTP and 30 microM 2MeSATP stimulation were observed. The response to UTP was reproducibly more sustained than that to 2MeSATP. 4. Stimulation of BAE cells with 100 microM UTP plus 30 microM 2MeSATP produced a response statistically indistinguishable from that predicted by addition of the responses to the two agonists in isolation. 5. The Ins(1,4,5)P3 response to UTP was attenuated to 25% of control by pretreatment of BAE cells with pertussis toxin. Responses to 2MeSATP and ADP were essentially unaffected. ATP stimulation was reduced to 65% of control. 6. Activation of protein kinase C with tetradecanoyl phorbol acetate (TPA) profoundly inhibited Ins(1,4,5)P3 responses to 2MeSATP and ADP but had no effect on UTP stimulation. The protein kinase C inhibitor, Ro 31-8220, enhanced responses to 2MeSATP, ADP and ATP but no effect was observed on UTP stimulation. 7. These observations show that nucleotide and P2Y-receptors mobilise the second messenger Ins(1,4,5)P3 by separate routes resulting in different patterns of generation and suggest that while ATP activates both receptors, ADP principally influences these cells by interacting with the P2Y-purinoceptors.
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PMID:Differential regulation of inositol 1,4,5-trisphosphate by co-existing P2Y-purinoceptors and nucleotide receptors on bovine aortic endothelial cells. 801 51

In these studies we show that stimulation of O2- generation by Tumor necrosis factor-alpha (TNF), or antibodies against the common beta 2 chain of leukocyte integrins (CD18), or LFA-1 (CD11a) displays a common and unique pattern of sensitivity or insensitivity to inhibitors of different signalling pathways. Both ways of stimulating neutrophil O2- generation were blocked by wortmannin, an inhibitor of myosin light chain kinase (Nakanishi, S., et al., 1992., J. Biol. Chem. 267, 2157-2163), and three different inhibitors of protein tyrosine kinases. Neither staurosporine, a protein kinase C inhibitor, nor Pertussis toxin, at concentrations which inhibited O2- generation in response to PMA, and FMLP, respectively, had any effect.
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PMID:Effect of inhibitors of distinct signalling pathways on neutrophil Q2- generation in response to tumor necrosis factor-alpha, and antibodies against CD18 and CD11a: evidence for a common and unique pattern of sensitivity to wortmannin and protein tyrosine kinase inhibitors. 809 58

The effect of purinergic receptor agonists on arachidonic acid release was investigated in [3H]arachidonic acid-prelabeled human airway epithelial cells. Exposure of bronchial epithelial BEAS39 cells to extracellular ATP resulted in a marked release of unesterified [3H]arachidonic acid with maximal effect observed within 60-90 s. [3H]diacylglycerol and [3H]phosphatidic acid accumulated in parallel with [3H]arachidonic acid. ATP-stimulated [3H]arachidonic acid release with a K0.5 of 9 +/- 2 microM and UTP was equipotent; no effect was observed with P2Y- or P2X-purinergic receptor agonists or with adenosine. Similar results were obtained with primary cultures of normal human nasal epithelium, CF/T43 and HBE1 airway epithelial cell lines derived from a cystic fibrosis patient and from a normal donor, respectively, and HT-29 human colon carcinoma cells. ATP stimulated inositol phosphate formation in BEAS39 cells with a concentration dependence identical to that for [3H]arachidonic acid release. The effect of ATP on both [3H]arachidonic acid release and inositol phosphate formation was equally inhibited by pertussis toxin. The Ca2+ ionophore A-23187 mimicked the effects of ATP or UTP on arachidonic acid release, and a marked inhibitory effect was observed with thapsigargin. The protein kinase C inhibitor staurosporine partially inhibited ATP-stimulated [3H]arachidonic acid release. These data are consistent with the hypothesis that phospholipase A2 activation is secondary to P2U-purinergic receptor stimulation of D-myoinositol 1,4,5-trisphosphate production and calcium mobilization from intracellular stores.
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PMID:Calcium-dependent release of arachidonic acid in response to purinergic receptor activation in airway epithelium. 814 Dec 54

Incubation of dispersed adenohypophyseal cells from intact male rats with Neuropeptide Y (NPY) or Peptide YY (YY) at 21 degrees C increased maximal 125I LHRHa binding (Bmax) by about 50%. In presence of 10(-7) M NPY, Bmax calculated from saturation isotherm curves was 15.3 +/- 1.9 fmoles x mg-1 proteins, as compared to 10 +/- 1 fmoles x mg-1 in control incubates. The increase was dose dependent with an EC50 of 6.3 +/- 1.8 10(-10) M NPY. Preincubation of the cells with pertussis toxin (PT, 15 ng/ml) for 24 h abolished the effect, suggesting coupling of NPY receptors to G alpha o or G alpha i proteins. NPY 10(-7) M inhibited basal and Forskolin 10(-5) M stimulated intracellular cyclic AMP formation by 31.9 +/- 3.4% and 30.6 +/- 2.3% respectively. Desensitization of protein kinase C by overnight preincubation of the cells with 10(-6) M phorbol ester (PMA) did not interfere with the effect of NPY. In contrast, W7, a calmodulin inhibitor, as well as H7, a protein kinase C inhibitor with a relatively wide spectrum, suppressed the effect of NPY with IC50 of 1.4 +/- 0.6 10(-6) M and 2.2 +/- 0.5 10(-5) M, respectively. Taken together, these results suggest that NPY is able to control unmasking of a cryptic LHRH receptor pool in pituitary cells by a process dependent upon both GTP binding proteins and calmodulin dependent protein kinase.
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PMID:Neuropeptide Y enhances LHRH binding to rat gonadotrophs in primary culture. 817 May 23

Cultured rat retinal pigment epithelium cells are shown to contain serotonergic, 5-HT2, receptors associated with phosphoinositide turnover and mobilization of intracellular calcium. Serotonin at a concentration of 10 microM induced a 2.5-fold increase in [3H]-inositol phosphates (more than 75% is in the form of [3H]-inositol-1-phosphate) accumulation within 30 min in cells preincubated in [3H]-myo-inositol and exposed to 5 mM lithium chloride. The EC50 value of serotonin was approx. 0.9 microM and the saturation concentration was 100 microM. Serotonin analogues like tryptamine, 5-methoxytryptamine, alpha-methyl-serotonin and the 5-HT2 agonists quipazine and DOI (1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane) all stimulated InsPs accumulation to some degree. Carbachol, noradrenaline, isoproterenol, dopamine, tryptophan, 5-hydroxytryptophan, 8-hydroxy-2(di-n-propyl-amino) tetralin, 2-methyl-serotonin and NECA (5'-[N-ethyl]-carboxamidoadenosine) were inactive. The serotonin-induced response was blocked most effectively by ketanserin and methysergide but not by 5-HT3 or 5-HT1 antagonists. The serotonin response was attenuated by the active phorbol ester, 4 beta-phorbol 12-myristate 13-acetate and this was attenuated by the non-selective protein kinase C inhibitor, staurosporine. Pertussis toxin failed to influence the serotonin-mediated phosphoinositide turnover. Addition of serotonin to cultures loaded with Fura-2 showed a transient increase in calcium concentrations in most of the cells. This change in calcium was independent of external calcium and the serotonin response was attenuated by ketanserin but not by the 5-HT3 antagonist granisetron.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotonergic, 5-HT2, receptor-mediated phosphoinositide turnover and mobilization of calcium in cultured rat retinal pigment epithelium cells. 827 84

Calcium, strontium and barium induced an exocytotic response in electropermeabilized rabbit neutrophils while magnesium was without any effect. The extent of enzyme release was found to depend upon the concentration of these cations. For all cations, an optimum concentration was found with the same maximum enzyme release. At concentrations higher than optimum a decrease in lysozyme release was observed. Efficiency to induce enzyme release was in the order: Ca2+ > Sr2+ > Ba2+. Enzyme release was significantly enhanced by guanosine-5'-[gamma-thio]triphosphate (GTP gamma S) resulting in a shift to the left of the dose/response curve. The enhancement by GTP gamma S was strongest with Ca2+, was less with Sr2+, and was very little with Ba2+. The time course of lysozyme release was the same for Ca2+, Sr2+, and Ba2+ in the presence and absence of GTP gamma S when suboptimal cation concentrations were used. A decrease in responsiveness to the effectors after electropermeabilization was observed with Ca2+, Sr2+ and Ba2+ in the presence and absence of GTP gamma S. The lysozyme release induced by the different cations was not inhibited by the protein kinase C inhibitor staurosporine and was slightly affected by pertussis toxin. Ca2+ and Sr2+, but not Ba2+, potentiated formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe) induced enzyme release in intact neutrophils. The divalent cation ionophore A23187 induced enzyme release in the presence of Ca2+ and Sr2+ but not in the presence of Ba2+. The results obtained with electropermeabilized neutrophils indicate that Sr2+ and Ba2+ can act as substitutes for Ca2+ in activating exocytosis, and that permeabilized neutrophils provide the best tool to investigate the effects of alkaline earth ions in exocytosis.
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PMID:Strontium and barium induce exocytosis in electropermeabilized neutrophils. 841 94

Conditions were established for the primary culture of guinea-pig tracheal smooth muscle cells, the identity of which was confirmed by the presence of smooth muscle alpha-actin by western blotting. Cells were preincubated with [3H]palmitate which was incorporated, almost exclusively, into phosphatidylcholine. When these cells were stimulated by either bradykinin or phorbol 12-myristate 13-acetate (PMA), in the presence of butan-1-ol, the non-metabolizable product [3H]phosphatidylbutanol ([3H]PtdBut) accumulated by virtue of the phosphatidyltransferase activity of phospholipase D. The activation of phospholipase D by bradykinin was inhibited by 86 +/- 11% (N = 3 experiments) in the presence of the protein kinase C inhibitor, staurosporine (1 microM) and by 88 +/- 11% (N = 3 experiments) in cells that had been chronically treated with PMA to down-regulate their protein kinase C. PMA-stimulated phospholipase D was similarly affected (92 +/- 2% inhibited by staurosporine, 87 +/- 6% inhibited by protein kinase C down-regulation). Removal of extracellular Ca2+ markedly reduced the bradykinin-stimulated phospholipase D response (by 73 +/- 10%, N = 3 experiments) but had only a limited effect upon PMA-stimulated phospholipase D activity (by 23 +/- 6%, N = 3 experiments). [AIF4](-)-stimulation of the cells also resulted in the activation of phospholipase D, indicating the involvement of a G-protein. However, this was not Gi since pertussis-toxin pretreatment of the cells failed to abolish either bradykinin-stimulated inositol (1,4,5)trisphosphate formation or [3H]PtdBut accumulation. Western blotting revealed the presence of Gq/G11 which couples to the inositol lipid-directed phospholipase C. Indomethacin (10 microM) was without effect upon bradykinin-stimulated phospholipase D activity, suggesting that the bradykinin effects were not mediated indirectly by cyclooxygenase products. The role of phospholipase D activation in tracheal smooth muscle may be to, indirectly, produce diacylglycerol for the activation of protein kinase C which has been implicated in sustained contraction. However, the immediate product of phospholipase D, phosphatidate, has been proposed to have a number of second messenger roles and may itself, by an undefined mechanism, be involved in the sustained contraction of airway smooth muscle.
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PMID:Bradykinin stimulates phospholipase D in primary cultures of guinea-pig tracheal smooth muscle. 844 59

Angiotensin II stimulates proximal tubule acidification by activating both the Na-H antiporter and the Na-HCO3 cotransporter. The mechanism whereby angiotensin II stimulates the Na-HCO3 cotransporter was investigated in renal cortical basolateral membrane vesicles of the rabbit by measuring 22Na uptake in the presence of HCO3 and gluconate. Na-HCO3 cotransporter activity (expressed in nanomoles per milligram of protein per 3 s) was taken as the difference in 22Na uptake in the presence of HCO3 and gluconate. Angiotensin II stimulated Na-HCO3 cotransporter activity significantly (control, 1.5 +/- 0.4; angiotensin II, 3.3 +/- 0.6; P < 0.05), and this stimulation was prevented by the angiotensin II receptor antagonist DuP 753. Angiotensin II has been shown to stimulate both pertussis toxin-sensitive Gi protein and pertussis toxin-insensitive Gq protein. In the presence of pertussis toxin, angiotensin II (10(-11) M) failed to stimulate the Na-HCO3 cotransporter, suggesting a role of Gi protein in mediating this effect. In the presence of a polyclonal antibody against Gi protein, angiotensin II failed to stimulate the Na-HCO3 cotransporter (control, 1.6 +/- 0.4; angiotensin II, 3.9 +/- 0.9; angiotensin II + Gi, 1.2 +/- 0.7). Angiotensin II stimulated inositol triphosphate release, and this effect could be blocked by the phospholipase C inhibitor U73122, suggesting a role of phospholipase C or A2 in this effect of angiotensin II. In the presence of the protein kinase C inhibitor calphostin C (50 nM), angiotensin II also failed to stimulate the Na-HCO3 cotransporter. These results demonstrate that angiotensin II stimulates the renal Na-HCO3 cotransporter by interacting with a specific angiotensin II receptor and that this stimulation is mediated by the activation of Gi and Gq proteins.
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PMID:Regulation of the renal Na-HCO3 cotransporter: IV. Mechanisms of the stimulatory effect of angiotensin II. 858 87

ADP evoked outwardly rectifying potassium currents with a latency of 0.6 s in cultured rat medullar neurons. Purinoceptor agonists, such as 2-methylthio ATP (2-MeSATP), ATP, AMP, alpha,beta-methylene ATP (alpha,beta-MeATP), and UTP, produced similar outward currents with the order of their potencies for current amplitudes: 2-MeSATP > ADP > ATP > or = alpha,beta-MeATP > or = AMP > UTP. This order corresponds to that for a subtype of P2Y purinoceptors. ADP-evoked currents were fully blocked by a broad G-protein inhibitor, guanosine-5'-O-(2-thiodiphosphate) (GDP beta S), whereas a G(i)/G(o)-protein inhibitor, pertussis toxin (PTX) had no effect. The currents were not affected by a phospholipase C (PLC) inhibitor, neomycin. Furthermore, a selective protein kinase C inhibitor, GF109203X or a selective cAMP-dependent protein kinase inhibitor, H-89 showed no effect on the currents. These results suggest that ADP activates the potassium channel via a P2Y purinoceptor linked to a PTX-insensitive G-protein and its channel regulation may be due to a direct action of the G-protein beta gamma subunits regardless of second messenger signaling cascades. Additionally, ADP enhanced intracellular free Ca2+ concentration ([Ca2+]i) both in the presence and absence of extracellular calcium, and this [Ca2+]i increase was not inhibited by neomycin. This provides an additional evidence that ADP binds to a subtype of P2Y purinoceptors, which is not involved in PLC stimulation.
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PMID:A P2 purinoceptor activated by ADP in rat medullar neurons. 859 44


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