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

Pasteurella haemolytica A1 culture supernatant containing leukotoxin, and modifiers of cyclic nucleotide and arachidonate metabolism, were evaluated for their ability to alter oxygen radical production by pulmonary alveolar macrophages obtained from seven Holstein calves. Calves were sedated, and underwent bronchoalveolar lavage to harvest macrophages, which were then incubated with culture supernatant and/or the drugs and toxins under study, and challenged with opsonized zymosan to induce oxygen radical generation. This was measured by a chemiluminescence technique. Pasteurella haemolytica A1 culture supernatant alone delayed the time to maximum oxygen radical production, although total production was increased. The cyclooxygenase inhibitor indomethacin and the phospholipase inhibitor p-bromophenacyl bromide significantly reduced maximum oxygen radical production, but their effects were diminished in the presence of culture supernatant. Although forskolin markedly inhibited oxygen radical generation, this effect was not altered by culture supernatant. Incubation of macrophages with pertussis toxin had no effect on oxygen radical production, while incubation with cholera toxin did inhibit production. This inhibitory effect was significantly lessened by concurrent incubation with P. haemolytica A1 culture supernatant.
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PMID:Effects of Pasteurella haemolytica A1 culture supernatant on mechanisms controlling bovine alveolar macrophage oxygen radical production. 235 60

Arachidonic acid is released from cell membranes in response to receptor-dependent as well as receptor-independent stimulation in various cells, including cardiac myocytes. Arachidonic acid is converted to prostaglandins by cyclooxygenase and to leukotrienes by 5-lipoxygenase, metabolites which are very biologically active and modulate cellular functions such as platelet aggregation, smooth muscle contraction and neural excitation. The molecular mechanisms underlying their modulations are, however, still badly understood. Here, we report that the 5-lipoxygenase metabolites of arachidonic acid activate the pertussis toxin-sensitive G protein-gated muscarinic K+ channel (IK.ACh): arachidonic acid activation of IK.ACh was prevented by the lipoxygenase inhibitors, nordihydroguaiaretic acid and AA-861; leukotriene A4 and C4 activated IK.ACh. The activation occurred in pertussis toxin-treated atrial cells and ceased when inside-out patches were formed but the patches were still susceptible to stimulation by GTP and to inhibition by GDP-beta-S. These results indicate that arachidonic acid metabolites may stimulate the G-protein in a receptor-independent way.
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PMID:Arachidonic acid metabolites as intracellular modulators of the G protein-gated cardiac K+ channel. 249 39

Muscarinic receptors of cardiac pacemaker and atrial cells are linked to a potassium channel (IK.ACh) by a pertussis toxin-sensitive GTP-binding protein. The dissociation of G-proteins leads to the generation of two potential transducing elements, alpha-GTP and beta gamma. IK.ACh is activated by G-protein alpha- and beta gamma-subunits applied to the intracellular surface of inside-out patches of membrane. beta gamma has been shown to activate the membrane-bound enzyme phospholipase A2 in retinal rods. Arachidonic acid, which is produced from the action of phospholipase A2 on phospholipids, is metabolized to compounds which may act as second messengers regulating ion channels in Aplysia. Muscarinic receptor activation leads to the generation of arachidonic acid in some cell lines. We therefore tested the hypothesis that beta gamma activates IK.ACh by stimulation of phospholipase A2. When patches were first incubated with antibody that blocks phospholipase A2 activity, or with the lipoxygenase inhibitor, nordihydroguaiaretic acid, beta gamma failed to activate IK.ACh. Arachidonic acid and several of its metabolites derived from the 5-lipoxygenase pathway, activated the channel. Blockade of the cyclooxygenase pathway did not inhibit arachidonic acid-induced channel activation. We conclude that the beta gamma-subunit of G-proteins activates IK.ACh by stimulating the production of lipoxygenase-derived second messengers.
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PMID:G-protein beta gamma-subunits activate the cardiac muscarinic K+-channel via phospholipase A2. 249 40

The present study and the previous report (6) show that the cyclooxygenase path is a primary route of metabolism of arachidonic acid in FRTL-5 rat thyroid cells. The production of PGD2 and PGE2 is an active process in intact cells treated with complete medium including TSH, insulin and 5% calf serum. In contrast, PGF2 alpha and HHT are probably nonenzymatic degradation products of an unstable intermediate, PGH2, since the two compounds are produced and occupy a significant proportion of the cyclooxygenase metabolites only in the homogenate system; this is true in other cells. Although the production of prostaglandins involves three steps, i.e. the release of free arachidonic acid, the production of PGH2 by PGH synthase (cyclooxygenase) and the conversion of PGH2 to various prostaglandins by specific isomerases or synthetases, the first step, the release of free arachidonic acid, has been, until recently, believed to be the sole step important for the regulation of prostaglandin synthesis. This presumption rested on the following observations. Only the free form of arachidonic acid is converted to prostaglandins and the intracellular free arachidonic acid pool is very small compared to the esterified form in phospholipids. The size of the free arachidonic acid pool is regulated by the balance between release from phospholipids by phospholipases and reacylation into phospholipids. When resting cells are stimulated, the release of arachidonic acid and the production of prostaglandins increase concomitantly. The present study shows, however, that all three steps of prostaglandin synthesis are under regulatory control in FRTL-5 rat thyroid cells and that the control is a complex process involving TSH, insulin/IGF-I, and serum. The first step is primarily under the control of TSH. TSH increases the synthesis of arachidonic acid and also, like norepinephrine (5, 6) induces the release of arachidonic acid from the cell by a mechanism involving a pertussis toxin-sensitive G protein. Regulation of the second step can be estimated by measuring cyclooxygenase activity. The present report shows that TSH increases cyclooxygenase activity, presumably by increasing gene expression, but that the TSH effect on cyclooxygenase activity requires insulin/IGF-I or serum. This result is similar to studies showing the effect of TSH and insulin/IGF-I on glycosaminoglycan synthesis, thyroglobulin synthesis, and growth in FRTL-5 thyroid cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The arachidonic acid signal system in the thyroid: regulation by thyrotropin and insulin/IGF-I. 251 71

alpha 2-Adrenoceptor agonists inhibit glucose-stimulated insulin release and glucose utilization in pancreatic islets. In isolated pancreatic islets of the rat, the Ca2+ channel agonists CGP-28392 and BAY-K-8644 increased insulin release in the presence of clonidine. Neither CGP-28392 nor BAY-K-8644 antagonized the effect of clonidine on glucose utilization. The Ca2+ ionophore, ionomycin, also did not affect glucose utilization in the presence or absence of clonidine. Glucagon partly reversed the effects of clonidine on insulin release, and it potentiated glucose-stimulated insulin release in the absence of clonidine. Glucagon reversed the effects of clonidine on glucose utilization. Amiloride antagonized the effects of clonidine on insulin secretion but did not enhance markedly glucose utilization in the presence or absence of clonidine. Carbamylcholine and arecoline reversed the effects of clonidine on glucose utilization and partly reversed the effects on insulin release in the absence of extracellular Ca2+. Prostaglandin (PG) E2, but not PGF2 alpha, inhibited glucose utilization in a time- and concentration-dependent manner. PGE2 also inhibited glucose-stimulated insulin release. Pertussis toxin blocked both actions of PGE2. The cyclooxygenase inhibitor indomethacin did not affect insulin release or glucose utilization in the presence of clonidine. Thus, elevated intracellular Ca2+ levels antagonize the effects of clonidine on insulin release, whereas other mediators appear to be required to alter glucose utilization.
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PMID:Calcium mobilization, prostaglandin E2 and alpha 2-adrenoceptor modulation of glucose utilization and insulin secretion in pancreatic islets. 254 83

Human erythroleukemia cells are a model system for studies of alpha 2-adrenergic receptors and their coupling to inhibition of adenylate cyclase (McKernan, R. M., Howard, M. J., Motulsky, H. J., and Insel, P. A. (1987) Mol. Pharmacol. 32, 258-265). Using Fura-2, we show that alpha 2-adrenergic receptor stimulation also increases intracellular Ca2+ in these cells by 80-250 nM. Although epinephrine only inhibited forskolin-stimulated cAMP generation when beta-adrenergic receptors were blocked, the Ca2+ increase was not affected by beta-adrenergic receptor blockade. The Ca2+ increase was not affected by forskolin or 8-bromo-cAMP. Thus, alpha 2-adrenergic receptors independently couple to elevation of intracellular Ca2+ and adenylate cyclase inhibition. Chelating all extracellular Ca2+ did not reduce the response, demonstrating mobilization of intracellular, rather than influx of extracellular Ca2+. The epinephrine-stimulated Ca2+ mobilization occurred prior to any detectable increase in inositol-(1,4,5)-trisphosphate. It was abolished by pretreatment with pertussis toxin (which blocks some G protein-mediated processes), but not by aspirin and indomethacin (which inhibit cyclooxygenase), nordihydroguaiaretic acid (which inhibits lipoxygenase), or Na+-free buffer (to block any Na+H+ exchange). We conclude, therefore, that alpha 2-adrenergic receptors on human erythroleukemia cells couple to mobilization of intracellular Ca2+ via a (pertussis toxin-sensitive) G protein-mediated mechanism that is independent of inhibition of adenylate cyclase.
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PMID:Alpha 2-adrenergic receptor stimulation mobilizes intracellular Ca2+ in human erythroleukemia cells. 256 96

Pertussis toxin (Ptx) has been employed as an adjuvant by many investigators to augment various types of cell-mediated and humoral immune responses. Recent work from our laboratory indicates that the exacerbation of delayed-type hypersensitivity (DTH) and contact hypersensitivity (CH) responses observed in Ptx-treated mice may be mediated by an absolute increase in the number of circulating neutrophils capable of migrating into tissue sites of antigen challenge. The purpose of the present study was to analyze the effects of Ptx on neutrophils and neutrophil function in vivo. Evidence is presented here suggesting that Ptx has both direct and indirect effects on neutrophils following its in vivo administration to normal mice. Mature neutrophils that are directly exposed to the actions of Ptx in vivo exhibit a marked reduction in their ability to extravasate into tissue sites of inflammation. These findings are consistent with those that have been reported following the exposure of isolated neutrophils to the effects of Ptx in vitro (i.e., that Ptx has an inhibitory effect on many of the functional capabilities of isolated neutrophils). Moreover, we have also determined that Ptx can affect the kinetics of neutrophil production indirectly through its ability to stimulate granulopoiesis. Ptx-exposed mice develop a protracted peripheral blood neutrophilia following toxin administration. Although the mechanism(s) involved in stimulating increased neutrophil production is presently unclear, both dexamethasone and indomethacin (cyclooxygenase pathway inhibitors) are able to function synergistically with Ptx to produce a markedly enhanced neutrophilia in exposed mice. We propose that the capacity of Ptx to augment CH and DTH responses and act as a potent adjuvant may relate, in part, to its ability to alter the rate of neutrophil production in vivo.
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PMID:Dual effects of pertussis toxin on murine neutrophils in vivo. I. Pertussis toxin inhibits extravasation potential of mature neutrophils while simultaneously stimulating granulopoiesis. 261 95

Epinephrine and norepinephrine (1-10 microM) stimulated the release of prostacyclin (PGI2) from the rabbit aorta in vitro. The stimulation was maintained for at least 2 h in the continuous presence of epinephrine. Phenylephrine mimicked this effect, whereas the selective alpha 2-agonist UK-14,304 was completely ineffective. The action of epinephrine was abolished by prazosin (1 microM) and was maintained in the presence of yohimbine. Epinephrine or phenylephrine neither increased the basal release of PGI2 from bovine aortic endothelial cells nor potentiated the stimulatory action of adenine nucleotides, which is mediated by P2-purine receptors. The response to epinephrine was lost in freshly deendothelialized strips of rabbit aorta, possibly because of cyclooxygenase self-inactivation. The response recovered however following overnight incubation of these strips in a cell culture medium. The response to epinephrine was mimicked by neither phorbol 12-myristate,13-acetate nor ionophore A23187. It was not inhibited by pretreatment with pertussis toxin. It is concluded that adrenergic agents stimulate the vascular production of PGI2, by activating alpha 1-receptors located on smooth muscle cells.
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PMID:Adrenergic stimulation of vascular prostacyclin: role of alpha 1-receptors in smooth muscle cells. 283 Jan 24

Addition of bombesin in the presence of either forskolin or cholera toxin caused a marked (4-6 fold) enhancement of cAMP accumulation in Swiss 3T3 cells. This effect was time and concentration dependent, induced by various bombesin-like peptides and blocked by a bombesin antagonist. Enhancement of cAMP accumulation by bombesin was diminished by chronic pretreatment with phorbol dibutyrate implicating the involvement of protein kinase C in the activation. Pretreatment with pertussis toxin, which uncouples protein kinase C activation from cAMP accumulation (Proc. Natl. Acad. Sci. U.S.A., 84:2282, 1987) also inhibited bombesin enhancement of cAMP. Bombesin was also shown to release E type prostaglandins into the medium, an effect which was abolished by the cyclooxygenase inhibitor indomethacin. Low concentrations (100 nM) of indomethacin partially inhibited the accumulation of cAMP by bombesin in the presence of forskolin indicating that the release of E type prostaglandins into the medium is also involved in the accumulation of cAMP by bombesin. The additive nature of PBt2-mediated down-regulation and treatment with indomethacin suggests that activation of protein kinase C and the release of E type prostaglandins provide two distinct pathways involved in the enhancement of cAMP accumulation by bombesin. Finally, bombesin in the presence of forskolin stimulated the phosphorylation of the intermediate filament component vimentin, identified in the accompanying paper as a substrate for a cAMP dependent protein kinase in intact Swiss 3T3 cells.
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PMID:Bombesin enhancement of cAMP accumulation in Swiss 3T3 cells: evidence of a dual mechanism of action. 284 40

Accumulation of inositol phosphates (Ins-Ps, revealed by high performance liquid chromatography), changes of the cytosolic free Ca2+ [( Ca2+]i, revealed by fura-2), membrane potential and ionic currents (revealed by bis-oxonol and patch clamping) were investigated in PC12 cells treated with bradykinin (BK). The phenomena observed were (a) due to the activation of a B2 receptor (inhibitor studies) and (b) unaffected by pertussis toxin, cAMP analogs, and inhibitors of either cyclooxygenase or voltage-gated Ca2+ channels. During the initial tens of s, three interconnected events predominated: accumulation of Ins-1,4,5-P3, Ca2+ release from intracellular stores and hyperpolarization due to the opening of Ca2+-activated K+ channels. Phorbol myristate acetate partially inhibited Ins-1,4,5-P3 accumulation at all [BK] investigated, and the [Ca2+]i increase at [BK] less than 50 nM. In PC12 cells treated with maximal [BK] in the Ca2+-containing incubation medium, Ins-1,4,5-P3 peaked at 10 s, dropped to 20% of the peak at 30 s, and returned to basal within 5 min; the peak increase of Ins-1,3,4-P3 was slower and was variable from experiment to experiment, while Ins-P4 rose for 2 min, and remained elevated for many min thereafter. Meanwhile, influx of Ca2+ from the extracellular medium, plasma membrane depolarization (visible without delay when hyperpolarization was blocked), and increased plasma membrane conductance were noticed. Evidence is presented that these last three events (which were partially inhibited by phorbol myristate acetate at all [BK]) were due to the activation of a cation influx, which was much more persistent than the elevation of the two Ins-P3 isomers. Our results appear inconsistent with the possibility that in intact PC12 cells the BK-induced activation of cation influx is accounted for entirely by the increases of either Ins-1,3,4-P3 or Ins-1,4,5-P3 (alone or in combination with Ins-1,3,4,5-P4), as previously suggested by microinjection studies in different cell types.
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PMID:Generation of inositol phosphates, cytosolic Ca2+, and ionic fluxes in PC12 cells treated with bradykinin. 314 20


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