UMLS:C0043167 - FACTA Search

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

Signaling via the alpha-beta T cell Ag receptor (Ti)-CD3 complex is a complicated event that implicates several protein kinases, most notably protein kinase C (PKC). We have recently identified a serine kinase in T lymphocytes with the following characteristics: molecular mass 43 kDa, in vitro substrate affinity for microtubule associated protein 2 (MAP-2) with a preference for Mn2+ during the catalytic reaction, and elution from DEAE resin over a salt range 100 to 200 mM NaCl. This kinase is activated in a rapidly reversible fashion during ligation of CD3/Ti by a process which involves prior phosphorylation; in vitro exposure of activated 43-kDa MAP-2 kinase (MAP-K) to an immobilized phosphatase abrogated its kinase activity. We now show that a MAP-2K response could also be obtained during treatment with mAb to Ti and the specific PKC agonist, PMA. Although the kinetics of the former response was rapidly reversible, PMA elicited a more prolonged response. The dose responsiveness for PMA was similar to the requirements for PKC activation in intact lymphocytes. Moreover, as with PKC, we found that the CD3-induced MAP-2K response could be further enhanced by using a second layer cross-linking antibody. The specificity of CD3/Ti in the Jurkat cell response is demonstrated by the fact that OKT-11(CD2) and anti-CD4 mAb did not stimulate a MAP-2K response. It was also not possible to elicit a response in a Jurkat cell mutant that lacks surface expression of CD3 and Ti. The specificity of PKC in these events was further explored with the cell permeant diacylglycerol, 1-oleoyl-2-acetylglycerol, and the nonagonist phorbol ester, 4 alpha-phorbol 12,13-didecanoate: whereas the former was an effective inducer of the MAP-2K response, the latter failed to yield any stimulation. Prior exposure of Jurkat cells to 100 mM PMA for 24 h eliminated greater than 60% of the MAP-2K response during anti-CD3 treatment. This response could also be inhibited in dose-dependent fashion by prior treatment of Jurkat cells with the potent PKC inhibitor 1-(5-isoquinolinesulfonyl) 2-methylpiperazine dihydrochloride. Although a Ca2(+)-ionophore failed to synergize with PMA at inducing a MAP-2K response, depletion of extracellular Ca2+ by EGTA abrogated anti-CD3 responsiveness. The events culminating in MAP-2K activation were slightly inhibited in the presence of cholera toxin but not pertussis toxin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Stimulation of MAP-2 kinase activity in T lymphocytes by anti-CD3 or anti-Ti monoclonal antibody is partially dependent on protein kinase C. 215 31

Preparations of rod outer segments from cattle retinas contained soluble and particulate phospholipase C activities which hydrolyzed phosphatidylinositol 4,5-bisphosphate (PIP2) and the other phosphoinositides. Ca2+ was required for PIP2 hydrolysis, but high (greater than 300 microM) concentrations were inhibitory. Mg2+ and spermine at low concentrations stimulated the particulate activity but inhibited the soluble. Mn2+ inhibited both. High (greater than 100 microM) concentrations of the nonhydrolyzable GTP analogue guanylyl beta,gamma-methylenediphosphonate inhibited PIP2 hydrolysis by both the soluble and particulate activities, but guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), fluoride, and cholera and pertussis toxins were without effect. Overall phospholipase C activity in ROS was unaffected by light. Evidence was found for multiple forms of the enzyme, requiring isolation and separate characterization before ruling out regulation by light or G-protein.
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PMID:Phosphatidylinositol-4,5-bisphosphate phospholipase C in bovine rod outer segments. 216 27

Agonist-stimulated divalent cation entry was studied in fura-2-loaded hepatocytes. In the presence of extracellular Mn2+, the Ca2(+)-mobilizing hormone vasopressin produced a severalfold stimulation of the basal rate of fura-2 fluorescence quenching as a result of Mn2+ influx; this effect was blocked by the presence of Ni2+ in the incubation medium. Half-maximum and maximum stimulation of Mn2+ influx was observed with 0.1 and 0.8 nM vasopressin, respectively. Agonist-stimulated Mn2+ influx was also seen with angiotensin II, ATP, phenylephrine, and the combination of AlCl3 and NaF. The stimulation of Mn2+ influx did not occur immediately after addition of Ca2(+)-mobilizing agents, but was characterized by a latency period of 20-30 s. In contrast to vasopressin, glucagon did not stimulate Mn2+ influx into hepatocytes, but produced both a 3-fold enhancement of the rate of vasopressin-stimulated Mn2+ entry and the abolishment of the latency period. The effects of glucagon were mimicked by forskolin and dibutyryl cAMP. Pretreatment of hepatocytes with pertussis toxin or depolarization of the cells altered neither the basal rate of Mn2+ entry nor the ability of vasopressin to stimulate this rate. Emptying of the inositol 1,4,5-trisphosphate-sensitive Ca2+ store by treatment with 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ) did not enhance Mn2+ entry into hepatocytes; however, exposure of the cells to tBuBHQ for 2 min markedly enhanced the ability of vasopressin, alone or in combination with glucagon, to increase the rate of Mn2+ influx. Furthermore, pretreatment with tBuBHQ for 2 min abolished the latency of vasopressin-stimulated Mn2+ influx. It is concluded that Ca2(+)-mobilizing hormones stimulate Ca2+ influx in hepatocytes, possibly through receptor-operated Ca2+ channels. The stimulation of divalent cation entry is transduced by a G protein, and the rate of influx appears to be controlled both by the intracellular level of cAMP and the empty state of an intracellular Ca2+ pool that may be inositol 1,4,5-trisphosphate-insensitive.
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PMID:Receptor-operated calcium influx in rat hepatocytes. Identification and characterization using manganese. 217 Mar 82

We recently reported that the secretagogue, compound 48/80, activated Ca2(+)-permeable channels of mast cells possibly via a second messenger [Kuno, Okada, and Shibata. Am. J. Physiol. 256 (Cell Physiol. 25): C560-C568, 1989]. The effects of pretreatment with pertussis toxin (PT) on compound 48/80 (48/80)-induced activation of the Ca2(+)-permeable channel have now been investigated by measuring Ca2+ signals of cell suspensions using the Ca2+ indicator fura-2 and by recording Ba2+ currents through the channel using the patch-clamp technique. In the presence of extracellular Ca2+, the fluorescence change was biphasic, with an immediate rise and a delayed peak at room temperature. The delayed peak, mainly due to Ca2+ entry through plasma membranes, was greatly reduced by pretreatment with PT. The quenching of the fluorescence by 48/80-induced Mn2+ influx was also decreased by PT, whereas the Ca2+ transients due to Ca2+ release from the intracellular stores apparently did not change. In patch-clamp recordings from cell-attached patches with pipettes containing isotonic Ba2+, the 48/80-induced Ba2+ currents were either suppressed or delayed in the PT-treated cells, under conditions where degranulation was absent. These results suggest that PT-sensitive GTP-binding protein is involved in activating the Ca2(+)-permeable channel in mast cells during stimulus-secretion coupling.
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PMID:PT pretreatment inhibits 48/80-induced activation of Ca(+)-permeable channels in rat peritoneal mast cells. 217 11

Leukotrienes are recognized as important mediators of the inflammatory process. Recently, increasing attention has been paid to the role of noninflammatory cells in the regulation of the inflammatory process. To further increase our knowledge of this matter we have, in the present study, investigated leukotriene-induced Ca2+ signaling, using a single cell technique in a human epithelial cell line, Intestine 407. It was evident that both LTD4 and LTE4, at physiological concentrations (10 nM), triggered rapid and pronounced cytosolic free Ca2+ transients, due to both influx across the plasma membrane and intracellular mobilization. Preincubation with pertussis toxin (1200 ng/ml) decreased the level of agonist-induced Ca2+ transients to an extent similar to that caused by depletion of extracellular Ca2+, suggesting that the toxin affected the influx but not the intracellular mobilization of Ca2+. Indeed, by using the Mn2+ quenching technique, it could be shown that pertussis toxin totally inhibited the influx of Ca2+. The fact that, even after pertussis toxin treatment, direct G-protein activation by AIF4- was still able to trigger a cytosolic free Ca2+ transient, indicates that, in these cells, G-proteins (GTP-binding proteins) that are insensitive to pertussis toxin are capable of mediating a Ca2+ signal. In order to test the idea that such G-proteins regulate mobilization of intracellular Ca2+ induced by LTD4 and LTE4, we electropermeabilized and preincubated the Intestine 407 cells with guanosine-5'-O-(2-thiodiphosphate) (GDP beta S), let them reseal, and, after loading with fura2, investigated the effects on agonist-stimulated Ca2+ signaling. Electropermeabiization and resealing alone did not significantly affect the Ca2+ responses triggered by LTD4 or LTE4. Addition of GDP beta S, in the presence of extracellular Ca2+, reduced the Ca2+ responses by approximately 60-70%. In Ca2(+)-depleted medium, GDP beta S also impaired the LTD4-induced response by 65%, however, it had no effect on the Ca2+ response induced by LTE4. In conclusion, LTD4 and LTE4 trigger cytosolic free Ca2+ signaling in a human epithelial cell line by causing both an influx of Ca2+ and mobilization of intracellular Ca2+. The Ca2(+)-signaling mechanism appears to consist of dual pathways, since the influx is regulated by a pertussis toxin-sensitive G-protein, but, the mobilization of Ca2+ is not. Furthermore, our data suggest that the LTD4-induced mobilization is regulated by a pertussis toxin-insensitive G-protein whereas the LTE4-induced mobilization is relatively insensitive to both pertussis toxin and GDP beta S.
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PMID:Leukotriene D4 and E4 induce transmembrane signaling in human epithelial cells. Single cell analysis reveals diverse pathways at the G-protein level for the influx and the intracellular mobilization of Ca2+. 217 31

Extracellular application of bradykinin and injection of inositol-1,4,5-trisphosphate (Ins-P3) induced a hyperpolarization in polyploid rat glioma cells. Ins-1,4,5-P3 and Ins-2,4,5-P3 were effective but not Ins-4,5-P2, Ins-1,3,4,5-P4 and Ins-1,3,4,5,6-P5. The reversal potential of the hyperpolarizing response induced by bradykinin or by Ins-P3 increased to a comparable degree with increasing the extracellular K+ concentration. Certain blockers of K+ channels, for example charybdotoxin (5-50 nM), Ba2+ (5-20 mM), 4-aminopyridine (5-10 mM) and quinidine (0.1-0.5 mM) reversibly suppressed the membrane potential response to bradykinin or to Ins-P3; however, apamin (1 microM) and D-tubocurarine (0.5 mM) had no effect. Intracellular injection of EGTA made the glioma cells unresponsive to bradykinin. Superfusion of the cells with Ca2(+)-free medium gradually and reversibly abolished the response to bradykinin, but only slightly reduced the effect of Ins-P3. The Ca2+ channel blockers Co2+ (1-5 mM), Mn2+ (2-6 mM) and nifedipine (1-20 microM), but not desmethoxyverapamil (100 microM) inhibited the hyperpolarizing effect of bradykinin. The hyperpolarization induced by Ins-P3, however, was not influenced by Mn2+ (1-5 mM) or by Co2+ (7 mM). Injection of Ca2+ into the glioma cells induced a hyperpolarization susceptible to Ba2+ and quinidine. Treatment of glioma cells with an activator or with inhibitors of protein kinase C or with pertussis toxin did not affect the response to bradykinin. Incubation of the cells with the Ca2+ ionophore A23187 (0.1-1 microM) made the cells unresponsive to bradykinin and, somewhat less, to Ins-P3. At these concentrations the Ca2+ ionophore primarily depletes intracellular Ca2+ stores. In summary, bradykinin, via B2-receptors (blocked by [Thi5,8, D-Phe7]-bradykinin) activates a K+ conductance in glioma cells following a rise of cytosolic Ca2+ activity most likely due to Ins-P3-mediated release of Ca2+ from internal stores. Entry of extracellular Ca2+ appears also to be involved in this process.
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PMID:Activation of a K+ conductance by bradykinin and by inositol-1,4,5-trisphosphate in rat glioma cells: involvement of intracellular and extracellular Ca2+. 230 62

2',5'-Dideoxyadenoside (DDA) inhibited both anti-IgE and ionophore A23187 induced histamine secretion from human basophils. Whereas DDA inhibited IgE-dependent histamine secretion when added at all times prior to challenge, release induced by A23187 was inhibited only with simultaneous addition of DDA and secretagogue. Dipyridamole, but not theophylline, abrogated DDA mediated inhibition of histamine release suggesting an intracellular mechanism of action of DDA. The observations that 2'-deoxyadenosine and 9-beta-D-arabinofuranosyladenine also inhibited release suggest that the its inhibitory effect was enhanced by manganese and reversed by islet activating protein from Bordetella pertussis suggest that DDA inhibits basophil histamine release by interacting with a guanine nucleotide binding protein which may be linked to either adenylate cyclase or other second messenger system(s).
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PMID:Inhibition of immunological and nonimmunological histamine release from human basophils by adenosine analogues that act at P-sites. 242 53

The aim of this study was to establish the mechanism by which adrenalectomy promotes the antilipolytic effect of the adenosine analog (-)-N6-(R-phenyl-isopropyl)adenosine (R-PIA) in rat fat cells. This action of adrenalectomy was not specific for R-PIA, since it was also observed with nicotinic acid and was prevented by phosphodiesterase inhibitors. In contrast, the inhibitory effect of R-PIA and nicotinic acid toward isoproterenol-stimulated cAMP accumulation was unaltered by adrenalectomy regardless of whether phosphodiesterase inhibitors were present. Whatever the conditions used, however, the cAMP levels in adrenalectomized rat adipocytes were one quarter to one third of those in sham-operated rats and remained below the limit over which variations in cAMP had no more influence in lipolysis. Both total and particulate low Km cAMP phosphodiesterase activities per adipocyte were decreased in adrenalectomized rats, but the stimulatory responses of the particulate enzyme to R-PIA remained unchanged. Pertussis toxin-catalyzed ADP ribosylation studies revealed a marked decrease in the total amount of the alpha-subunits of Go and the adenylate cyclase inhibitory regulatory protein Gi after adrenalectomy. However, the inhibitory dose-response curves of adenylate cyclase to R-PIA, nicotinic acid, GTP, guanylylimidodiphosphate, and guanosine 5'-O-(3-thiotriphosphate) were unaltered by adrenalectomy, indicating that the inhibitory function of Gi is unimpaired by adrenalectomy. Lastly, adrenalectomy resulted in a 60% reduction of the Mn2+-stimulated adenylate cyclase activity/adipocyte, which indicates that adrenalectomy causes a defect in adenylate cyclase catalytic activity. Thus, enhanced antilipolytic effects of R-PIA induced by adrenalectomy do not involve increased function of the adenosine receptor Gi-coupled adenylate cyclase inhibitory pathway, but are related to abnormally low intracellular cAMP levels due to defective adenylate cyclase catalytic activity.
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PMID:Role of adenosine 3',5'-monophosphate and the Ri-receptor Gi-coupled adenylate cyclase inhibitory pathway in the mechanism whereby adrenalectomy increases the adenosine antilipolytic effect in rat fat cells. 246 35

The ontogenesis of alpha 2-adrenoceptors and GTP-binding proteins and their coupling activity were investigated in telencephalon membranes of developing rats. The manganese-induced elevation of [3H]clonidine binding was increased in an age-dependent manner but the guanosine 5'-O-(3-thio)triphosphate-induced decrease in binding did not change. The extent of the binding of [3H]clonidine at 15 nM (saturable concentration) increased in an age-dependent manner and reached the adult level at 4 days after birth. Cholera toxin and pertussis toxin catalyzed ADP-ribosylation of proteins of 46 and 41/39 kilodaltons (kDa) in solubilized cholate extracts of the membranes. The 41/39-kDa proteins ADP-ribosylated by pertussis toxin (Gi alpha + Go alpha) were increased with age and reached the adult level at day 12, whereas the 46-kDa protein (Gs alpha) reached its peak on day 12 and then decreased to the fetal level at the adult stage. The immunoblot experiments of the homogenates with antiserum (specific antibody against alpha- and beta-subunit of GTP-binding proteins) demonstrated that the 39-kDa alpha-subunit of (Go alpha) and the 36-kDa beta-subunit of GTP-binding protein (beta 36) increased with postnatal age. In contrast, 35-kDa beta-subunit (beta 35) did not change. From these results, it is suggested that the coupling activity of alpha 2-adrenoceptor with GTP-binding protein gradually develops in a manner parallel with the increase of alpha 2-adrenoceptor and pertussis toxin sensitive GTP-binding proteins, Gi, and that alpha 39 beta 36 gamma may be related to the differentiation and/or growth of nerve cells in rat telencephalon.
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PMID:Ontogenesis of alpha 2-adrenoceptor coupling with GTP-binding proteins in the rat telencephalon. 254 60

Leukemic cell growth in the marrow microenvironment may be modulated by stromal cell products, including stimulatory growth factors and the inhibitory regulator prostaglandin E. The production of both of these stromal cell products induced by cytokine mediators appears to be closely linked. Cyclic AMP (cAMP) is an intracellular second messenger that inhibits myeloid cell proliferation and is produced in myeloid leukemia cells on stimulation of adenylate cyclase enzyme by prostaglandin E1 (PGE1). Cells expressing the product of an RAS oncogene have been observed to display diminished hormone-stimulated adenylate cyclase of membranes. If this observation were applicable to myeloid cells, a potentially important mode for leukemia cells expressing p21 RAS to escape inhibitory regulation within the hematopoietic microenvironment would be identified. We studied an interleukin-3 (IL-3)-dependent myeloid cell line, NFS/N1.H7, and a derivative line transfected with H-RAS codon 12 (T24) oncogene, H7 Neo Ras.F3, for inhibition of proliferation by PGE1, 1 microM, alone or in combination with pertussis toxin, which inactivates Gi, an inhibitory regulatory guanosine triphosphate (GTP)-binding protein of adenylate cyclase. NFS/N1.H7 cells were inhibited in interleukin-3-dependent proliferation (dose range, IL-3 10 to 100 U/mL) by PGE1 79 +/- 11%, by pertussis toxin 51 +/- 9%, and by the combination 92 +/- 2%, whereas H7 Neo RAS.F3 was inhibited 51 +/- 7%, 6 +/- 2%, or 58 +/- 9% by PGE1, pertussis toxin, and the combination, respectively. These differences in capacity for inhibition by adenylate cyclase agonists between RAS-transfectant cells (lower inhibition) versus parent cells (greater inhibition) were all highly significant (P less than .0005). Intracellular cAMP formed on PGE1 stimulation of pertussis-intoxicated cells was 150% lower in RAS-transfectant cells than in parent cells. The adenylate cyclase activity of membranes from pertussis-intoxicated RAS-transfected cells was 1.5 to two times lower than that of pertussis-intoxicated parent-cell membranes on Mg2+-dependent activation by hormone and/or guanine nucleotide. However, very similar adenylate cyclase activity was observed in oncogenic p21 RAS-containing membranes compared with parental membranes under conditions of direct activation by 4 mM Mn2+ and forskolin, where inhibitory or stimulatory G-protein influences are minimal. These studies showed diminished adenylate cyclase activity in mutant RAS-bearing myeloid-cell membranes compared with parent-cell membranes independent of the pertussis toxin-sensitive G protein, Gi.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effector function for RAS oncogene in interleukin-3-dependent myeloid cells involves diminished efficacy of prostaglandin E1-mediated inhibition of proliferation. 267 12

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