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)

A human polymorphonuclear leukocyte (PMN) activating factor (AFH-S) was isolated from a tropical plant seed, Aleurites Fordii Hemsl. (AFH) in PBS. It is found that the AFH-S stimulate human PMNs and induced superoxide generation and chemotaxis. Superoxide generation was affected by the extracellular calcium ion or pretreatment with H-7 (PK-C inhibitor), but not by mepacrine (PLA2 inhibitor) or pertussis toxin (islet-activating protein: IAP). Furthermore, a lag time exists dose-dependently. In addition the cytosolic calcium was not increased by the stimulation with AFH-S. Thus, the receptor for AFH-S was suggested to be independent from Ni-like protein, PI-response, or PLA2-activation, and stimulate PMNs through activation of PK-C.
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PMID:Human polymorphonuclear leukocyte activating factor isolated from Aleurites Fordii Hemsl. (Euphorbiaceae) seed. 285 81

In pre-labelled A549 cells epidermal growth factor (EGF) (10 nM) stimulates the release of [5,6,8,9,11,12,14,15-3H(N)]-arachidonic acid (3H-AA) by approximately 70%. Increasing Ca2+i with thapsigargin (50 nM) stimulates 3H-AA release by approximately 120%. However, the combined use of these two agents results in a synergistic stimulation of 3H-AA release by over 700%. The EGF stimulated release is sensitive to pertussis toxin (10 ng/mL) and guanosine 5'-O-(2-thiodiphosphate) suggesting a G protein-mediated event. This is supported by the fact that the G protein activators AlF-4 and guanosine 5'-O-(2-thiotriphosphate) both stimulate 3H-AA release. The stimulation of 3H-AA release by both EGF or direct G protein activation is completely blocked following pre-treatment for 3 hr with 1 nM dexamethasone. This effect is reversed with a neutralizing antibody to lipocortin-1 (1 microgram/mL) suggesting that this protein mediates the inhibitory effects of glucocorticoids on agonist activated 3H-AA release. Thapsigargin stimulation of 3H-AA release is insensitive to dexamethasone treatment. A peptide fragment from the N-terminus of lipocortin-1-Lc13-25 (20-200 micrograms/mL) mimics the effect of glucocorticoid in suppressing both EGF and G protein activated 3H-AA release. A peptide with Me-Tyr substituting Tyr21 is much reduced in activity suggesting that the presence of this residue is essential. As peptide Lc13-25 is not derived from the Ca2+/phospholipid binding domain of the native protein then sequestration of phospholipid substrate for PLA2 remains an unlikely mechanism of action for this peptide.
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PMID:Lipocortin-1 and the control of arachidonic acid release in cell signalling. Glucocorticoids (changed from glucorticoids) inhibit G protein-dependent activation of cPLA2 activity. 764 51

The regulation of phospholipase A2 by G protein-coupled receptors is examined in CHO cells which normally express the purinergic receptor and have been transfected with bovine rhodopsin. The purinergic receptor has been reported to activate both phospholipase C and phospholipase A2 in this cell line. In contrast, bovine rhodopsin by itself is not able to activate phospholipase A2. However, the photoreceptor does potentiate purinergic receptor-mediated phospholipase A2 activation in a light-dependent manner. Both the purinergic receptor stimulation of phospholipase A2 and the enhanced activity mediated by rhodopsin are completely pertussis toxin-sensitive, suggesting the regulation of phospholipase A2 by a member of the Gi family of G proteins. Both of these receptors also inhibit adenylyl cyclase activity. Rhodopsin-mediated inhibition of adenylyl cyclase is pertussis toxin-sensitive, whereas inhibition by the purinergic receptor is calcium-sensitive but not pertussis toxin-sensitive. These results suggest (1) that rhodopsin is similar to other receptors that normally couple to Gi when expressed in cultured cells and (2) that regulation of adenylyl cyclase and PLA2 in CHO cells by rhodopsin and the purinergic receptor occur via distinct pathways.
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PMID:The coupling of pertussis toxin-sensitive G proteins to phospholipase A2 and adenylyl cyclase in CHO cells expressing bovine rhodopsin. 781 32

In cultured cells the cytopathic effects (CPE) of Clostridium difficile toxins A and B are superficially similar. The irreversible CPEs involve a reorganization of the cytoskeleton, but the molecular details of the mechanism(s) of action are unknown. As part of the work to elucidate the events leading to the CPE, cultured cells were preincubated with agents known to either stimulate or inhibit some major signal transduction pathways, whereupon toxin was added and the development of the CPE was followed. Both toxin-induced CPEs were enhanced by phorbol esters and mezerein, which stimulate protein kinase C, while they were inhibited by the phospholipase A2 inhibitors quinacrine and 4-bromophenacylbromide. Agents affecting certain G-proteins, cGMP and cAMP levels, phosphatases, prostacyclin, lipoxygenase, and phospholipase C did not affect the development of the CPE of either toxin. Thus, the cytoskeletal effect induced by toxins A or B appears to require PLA2 activity and involves at least part of a protein kinase C-dependent pathway, but not pertussis toxin-sensitive G-proteins, cyclic nucleotides, eicosanoid metabolites, or phospholipase C activity. In addition, both toxins were shown to activate phospholipase A2.
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PMID:Signal transduction pathways and cellular intoxication with Clostridium difficile toxins. 832 Feb 69

We have characterized the signaling pathways of purinergic receptors present on the renal epithelial cell line, Madin-Darby canine kidney (MDCK, D1 subclone). Several lines of evidence are consistent with the conclusion that coexisting P2u and P2y receptors release arachidonic acid and metabolites (AA) from MDCK-D1 cells: 1) relative potencies of nucleotide analogues, 2) blockade of P2y agonist- but not P2u agonist-mediated release by suramin, and 3) additivity by 2-methylthio-ATP and UTP. Differences exist between the signaling pathways of the two receptors: pertussis toxin treatment partially inhibits P2u- but not P2y-mediated AA release, and P2y (but not P2u) receptors appear to stimulate D-myo-inositol 1,4,5-trisphosphate production. P2u-receptor occupancy results in both homologous and heterologous desensitization; P2y-receptor occupancy elicits only homologous desensitization. Both receptors stimulate phosphatidylcholine hydrolysis via phospholipase C activation. However, AA release appears to result from phospholipid deacylation by phospholipase A2 activation, rather than from alternate pathways that may include PLC activation. These results demonstrate for the first time that two subtypes of P2-purinergic receptors, P2u and P2y receptors, coexist on a single renal epithelium cell type and that these two receptor subtypes can promote AA release, probably via activation of PLA2.
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PMID:Heterogeneity of P2u- and P2y-purinergic receptor regulation of phospholipases in MDCK cells. 885 23

Low concentrations of angiotensin II (Ang II) increase, whereas high concentrations inhibit the apical Na/H antiporter activity in the proximal tubule, but the respective roles of the different signaling pathways in mediating these effects remains unsettled. We studied the effects of both low and high doses of Ang II in the presence of selective signaling pathway inhibitors, on the apical Na/H antiport activity of rat proximal tubule. Experiments were carried out in intact cells of freshly prepared tubule fragments obtained from the outer third of cortex, that is, devoid of basolateral Na/H antiport activity in the absence of bicarbonate transport and H(+)-ATPase activity. In tubules acid-loaded by an NH4Cl prepulse, Na/H antiport activity was assessed by the initial rate of intracellular pH recovery (dpHi/dt), measured with BCECF. When tubules were preincubated with low dose Ang II (10(-11) M for 3 min), dpHi/dt increased by 25 +/- 8%, whereas incubation with high dose Ang II (10(-7) M for 3 min) decreased dpHi/dt by 30 +/- 4%, compared to control (P < 0.01 in both cases). Both effects were abolished in the presence of 2.10(-3) M amiloride. Low dose Ang II-induced increase in dpHi/dt was not affected by preincubation with a specific PKA inhibitor, Rp-CPT-cAMP 10(-4) M, and was completely abolished by preincubation with PKC inhibitors, staurosporine 10(-7) M, sphingosine 5.10(-6) M, or calphostin 10(-6) M. In addition, pretreatment of rats with pertussis toxin led to a partial inhibition of the effect of low dose Ang II. The high dose-Ang II-induced decrease in dpHi/dt was not affected by pretreatment with a calcium-calmodulin kinase inhibitor W-7 10(-4) M. Conversely, pretreatment with the cytochrome P-450 inhibitor econazole 10(-5) M reversed the inhibitory effect of high dose Ang II to a stimulatory effect (24 +/- 8%, P < 0.01), quantitatively similar to the effect of low dose Ang II. In addition, arachidonate was found to exert an econazole-sensitive dose-dependent inhibitory effect on dpHi/dt, and 5,6-EET 10(-6) M, a cytochrome P-450 derived-arachidonic acid metabolite, induced a 38 +/- 9% inhibition, similar to that observed with high dose Ang II alone. There was no additive effect of 5,6-EET and high dose Ang II. Finally, pretreatment with two PLA2 inhibitors (BromoPhenacylBromide, 6.10(-6) M, and oleyloxyethyl phosphorylcholine, 5.10(-6) M) reversed the inhibitory effect of high dose Ang II to a stimulatory effect (32 +/- 11% and 25 +/- 11%, respectively, P < 0.05 for both inhibitors). We conclude that, in intact rat proximal cells, low dose Ang II stimulates the apical Na/H antiport through a pertussis toxin-sensitive G protein-dependent PKC pathway, whereas high dose Ang II inhibits the Na/H antiport activity through the PLA2- and cytochrome P-450-dependent metabolites of arachidonate.
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PMID:Signaling pathways in the biphasic effect of angiotensin II on apical Na/H antiport activity in proximal tubule. 891 15

Condensed tannin, isolated from cotton bracts extract (CBE), increases arachidonic acid (AA) release from rabbit alveolar macrophages and inhibits its subsequent reacylation. We determined whether tannin from CBE had any effect upon AA release in bovine tracheal epithelial cells (BTE). [14C] AA release was measured at timed intervals after addition of various concentrations of tannin to BTE cells grown to confluence in the presence of [14C] AA. Tannin caused a time- and dose-dependent release of AA from airway cells, with a maximum release occurring at 1 min in the presence of 100 micrograms/ml of tannin, and was confirmed by high-pressure liquid chromatography. The pattern of release was similar to that observed with bradykinin (2 x 10(-6) M). AA release by tannin was partially inhibited by indomethacin (10(-5) M) but not by 5,8,11,14-eicosatetraynoic acid (ETYA; 10(-5) M. Both of these drugs were effective in inhibiting bradykinin-induced AA release. In addition, AA release was not inhibited by cycloheximide. Endotoxin at 100 pg/ml and higher also caused a time-dependent release of AA that was not inhibitable by indomethacin or ETYA. Tannin-induced AA release was inhibited by pretreatment with pertussis toxin but not by neomycin, an inhibitor of phospholipase C (PLC). Neither pertussis toxin nor neomycin had any effect upon endotoxin-induced AA release. In other experiments, neither tannin nor endotoxin had any effect on [14C]AA uptake by BTE. These data demonstrate that tannin at low concentrations and endotoxin at high concentrations increase AA release by BTE cells. The AA release by tannin is partially metabolized by the cyclooxygenase pathway. We hypothesize that tannin-induced AA release is not mediated by PLC but may be mediated by other phospholipases, including PLA2.
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PMID:Tannin stimulates arachidonic acid release from bovine tracheal epithelial cells. 892 21

The present study investigated the role of kinases and G-proteins in arachidonic acid (AA) mobilization by resident mouse peritoneal macrophages in response to phagocytosis of opsonized zymosan. Stimulation of resident murine peritoneal macrophages with opsonized zymosan caused an increase in [3H] arachidonic acid release. This increase was dose-dependent and was not accompanied by de novo synthesis of proteins. Neither staurosporine, a protein kinase C inhibitor, nor genistein, a tyrosine kinase inhibitor, had any effect on [3H] AA mobilization, although trifluoperazine significantly inhibited AA release. The involvement of G proteins and phospholipase C (PLC) in the regulation of arachidonic acid release induced by opsonized zymosan was also examined in mouse peritoneal macrophages. Prior treatment of cells with pertussis toxin induced a partial decrease in AA mobilization. However, neomycin or aspirin, at doses that inhibit inositol phosphate formation (PLC activity), did not [3H] AA mobilization by PLA2. We proposed that the AA release by peritoneal macrophages in response to opsonized zymosan phagocytosis could be due to the participation of enzymes other than PLC and PKC, or proteins other than G proteins.
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PMID:Role of kinases and G-proteins on arachidonate release induced by zymosan in mouse peritoneal macrophages. 902 57

Occupancy of oxytocin receptor (OTR) binding sites in pregnant rat myometrial membranes with iodinated oxytocin antagonist (OTA), followed by detergent solubilization and size selection, showed that radioactivity eluted in two distinct peaks: one corresponding in size to the isolated receptor (approximately 60 kDa) and the other ranging from 240 to 320 kDa. The unliganded 240- to 320-kDa fraction contained OTRs coupled to G proteins, as the addition of oxytocin (OT) increased guanosine 35S-labeled 5'-O-(3-thiotriphosphate) binding up to twofold in a dose-dependent manner. The effects of OT were blocked by coincubation with OTA. G protein alpha-subunits associated with OTRs in the 240- to 320-kDa peak were identified by immunoadsorption. Significant amounts of both G alpha q/11 and G alpha i3 were associated with the OTR; a lesser amount of G alpha s was complexed. Using the same approach but with antibodies to effector enzymes, we observed that phospholipase C beta 1 (PLC beta 1) and PLA2 were also associated with the OTR. The results corroborate the well-established interaction of OTR with Gq and further show that Gi coupling might be an important component of OTR signal transduction. To further investigate the interaction of Gi with the OTR, we showed that OT stimulation of guanosine 5'-triphosphatase activity in intact myometrial membranes was inhibited by pertussis toxin. Pertussis toxin-stimulated ADP ribosylation of G alpha i in myometrial membranes was also decreased by OT treatment. These findings with pertussis toxin strongly indicate that OTR is coupled to Gi in rat myometrial membranes. The 60-kDa OTR peak (noncoupled receptor) was demonstrable in the myometrium only before the end of gestation and after parturition and accounted for about one-half the 125I-OTA binding activity. At term, there was about a fivefold increase in binding and almost a complete shift to the 240- to 320-kDa-size complex. Thus the established increased sensitivity of the myometrium to OT at term could be the result of both upregulation of OTRs and an increase in the fraction of receptors coupled to signal transduction components, one of which is Gi.
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PMID:Coupling of oxytocin receptor to G proteins in rat myometrium during labor: Gi receptor interaction. 917 88

Vascular smooth muscle cells (SMCs) can be induced to proliferate in response to several cytokines and growth factors, including interleukin (IL)-6. Platelet-activating factor (PAF) also has been shown to induce SMC proliferation. Because PAF can stimulate IL-6 production in monocytes, macrophages, and endothelial cells, our study was undertaken to determine whether PAF could induce IL-6 production by SMCs and to define the underlying signaling pathways. Exposure of rat aortic SMCs to picomolar concentrations of PAF resulted in enhanced production of IL-6. The effect was concentration dependent, selective for the active form of PAF, and mediated by specific PAF receptors. Pretreatment of the cells with Bordatella pertussis toxin (PTX) prevented the effect of PAF, suggesting the involvement of alpha i-type subunits of G proteins in the signal-transduction pathway. PAF-dependent IL-6 production was also prevented by inhibition of tyrosine kinases with genistein or erbstatin. Inhibition of eicosanoid production by blocking either phospholipase A2 or cyclooxygenase also abrogated the effect of PAF on IL-6 production. Moreover, inhibition of Ca2+-calmodulin activity with W7 or blocking of calcium channels with verapamil or nifedipine prevented PAF-mediated enhancement of IL-6 production. Whereas PAF-induced signal-transduction pathways leading to IL-6 production and SMC proliferation were partially common, they appeared to diverge downstream of PLA2 activation: inhibition of cyclooxygenase had no effect on proliferation, whereas augmentation of cyclic adenosine monophosphate (cAMP) levels or activation of protein kinase A inhibited proliferation, in contrast to IL-6 production. Our findings suggest a role for PAF in modulating vascular function by stimulating local production of IL-6 by SMCs and promoting their proliferation. The two effects are, however, associated with partially divergent signaling pathways and may not be causally related.
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PMID:Differential signaling pathways in platelet-activating factor-induced proliferation and interleukin-6 production by rat vascular smooth muscle cells. 926 43


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