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)

The outputs of prostaglandin (PG) F-2 alpha, 6-keto-PGF-1 alpha and PGE-2 from Day-7 and Day-15 guinea-pig endometrium were neither stimulated nor inhibited by cholera toxin and pertussis toxin. This indicates that PG synthesis by guinea-pig endometrium is not controlled by toxin-sensitive G-proteins. Short-term treatment of guinea-pig endometrium in culture with sodium fluoride stimulated PG output, suggesting that endometrial PG synthesis may be regulated by a fluoride-sensitive G-protein. Long-term treatment of guinea-pig endometrium in culture with sodium fluoride inhibited endometrial PG synthesis, and this was due to an inhibition of endometrial protein synthesis. Human alpha-interferon had no inhibitory effect on the outputs of PGF-2 alpha, 6-keto-PGF-1 alpha and PGE-2 from Day-15 guinea-pig endometrium in culture. It appears that the anti-luteolytic factor secreted by guinea-pig conceptus is not an alpha-interferon and is therefore probably different from ovine trophoblast protein-1.
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PMID:The effects of cholera toxin, pertussis toxin, sodium fluoride and alpha-interferon on prostaglandin production by the guinea-pig endometrium. 237 26

We previously reported that prostaglandin F2 alpha (PGF2 alpha) receptor is coupled to pertussis toxin (PTX)-sensitive GTP-binding protein (G protein) in osteoblast-like MC3T3-E1 cells [Miwa et al. (1990): Biochem Biophys Res Commun 171:1229-1235]. In the present study, we examined the effect of PGF2 alpha on the activation of phosphatidylcholine-hydrolyzing phospholipase D in MC3T3-E1 cells. PGF2 alpha stimulated the formation of choline in a dose-dependent manner in the range between 10 nM and 10 microM. The formation of choline was stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C (PKC)-activating phorbol ester. 4 alpha-Phorbol 12, 13-didecanoate, a PKC-nonactivating phorbol ester, had little effect on choline formation. The formation of choline stimulated by a combination of PGF2 alpha and TPA was additive. Staurosporine, an inhibitor for protein kinases, which inhibited the effect of TPA on choline formation, dose-dependently enhanced the formation of choline induced by PGF2 alpha. NaF, an activator of G protein, stimulated the formation of choline. The formation of choline stimulated by a combination of PGF2 alpha and NaF was not additive. NaF-induced formation of choline was dose-dependently enhanced by staurosporine. PTX dose-dependently inhibited the PGF2 alpha-induced formation of choline. These results strongly suggest that PGF 2 alpha activates phospholipase D independently from the activation of PKC in osteoblast-like cells and PTX-sensitive G protein is involved in the PGF2 alpha-induced phospholipase D activation.
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PMID:Prostaglandin F2 alpha activates phospholipase D independently from activation of protein kinase C in osteoblast-like cells. 796 70

The present study was conducted to localize and characterize the subtype(s) of muscarinic receptor involved in prostacyclin production elicited by the cholinergic transmitter acetylcholine (ACh) in various cell types in the rabbit heart. ACh increased prostacyclin synthesis, measured as 6-keto-prostaglandin(1 alpha) (6-keto-PGF(1 alpha)), in cultured coronary endothelial cells and freshly dissociated ventricular myocytes in a dose-dependent manner, but not in cultured coronary smooth muscle cells of rabbit heart. McN-A-343 {(4-hydroxy-2-butynyl)-1-trimethylammonium-m-chlorocarbanilate chloride}, a selective M1 muscarinic ACh receptor (mAChR) agonist, did not alter 6-keto-PGF(1 alpha) synthesis in these cell types. ACh induced 6-keto-PGF(1 alpha) synthesis in coronary endothelial cells and ventricular myocytes was not altered by a low concentration (0.01 microM) of pirenzepine, an M1 mAChR antagonist, but was reduced by a higher concentration (1 microM). In coronary endothelial cells, ACh-induced 6-keto-PGF(1 alpha) production was reduced by hexahydrosila-difendial (HHSiD), an M3 mAChR antagonist, and in ventricular myocytes by both AF-DX 116 [11-{2-[(diethylamino)methyl]-1-piperidinyl]acetyl-5,11-dihydro-6H- pyrido[2,3-b]-benzodiazepine-6 one}], an M2 receptor antagonist, and HHSiD. The decrease by ACh of isoproterenol-stimulated cAMP accumulation was minimized by AF-DX 116, but not by HHSiD or pirenzepine. Pertussis toxin treatment minimized ACh-induced decrease in isoproterenol-stimulated rise in cAMP, but not ACh-induced 6-keto-PGF(1 alpha) synthesis. These data suggest that ACh stimulates prostacyclin production in coronary endothelial cells via M3 mAChR and in ventricular myocytes via M2 and M3 mAChR, and may contribute to its cardioprotective effects. Moreover, ACh induced decrease in cAMP, but not the increase in 6-keto-PGF (1 alpha) production, is mediated by pertussis toxin-sensitive G(alpha i) proteins in these cells.
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PMID:Localization and characterization of the subtypes(s) of muscarinic receptor involved in prostacyclin synthesis in rabbit heart. 878 73

Spontaneous tone of in vitro lower esophageal sphincter (LES) circular muscle is associated with elevated levels of arachidonic acid (AA), PGF(2alpha), and increased [35S]guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) binding to Gq-, Gi3-, and G(i1/i2)-like G proteins. Tone and AA levels were reduced by inhibitors of a pancreatic-like (group I) secreted phospholipase A2 (sPLA2), by the cyclooxygenase inhibitor indomethacin, and by the thromboxane A2 antagonist SQ-29548. In addition, pertussis toxin (PTX) reduced LES tone, confirming a role of PTX-sensitive G proteins in maintenance of LES tone. PGF(2alpha) contracted LES smooth muscle (strips and cells) and increased [35S]GTPgammaS binding to Gq and Gi3 in solubilized LES circular muscle membranes. PGF(2alpha)-induced contraction of LES permeable muscle cells was inhibited by Gq and Gi3 but not by G(i1/i2) and Go antibodies. The thromboxane A2 analog U-46619 contracted LES smooth muscle and increased Gq binding. U-46619-induced contraction was inhibited by Gq but not by Gi3, G(i1/i2), and Go antibodies. LES tone and [(35)S]GTPgammaS binding were significantly reduced by indomethacin. We conclude that group I sPLA2 may mediate "spontaneous" LES tone by producing AA, which is metabolized to PGF(2alpha) and thromboxane A2. These AA metabolites activate receptors linked to Gi3 and Gq to maintain LES contraction.
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PMID:Group I secreted PLA2 and arachidonic acid metabolites in the maintenance of cat LES tone. 1048 84

We have developed a high yield technique for isolating ventricular myocytes from adult mouse hearts. This collagenase-trypsin procedure yields 3-6x10(6)cells/heart. The cells are rod-shaped, roughly 20 microM x 100 microM and Ca(++)tolerant, with viability of 65-80%. Binding studies with [(125)I]ICYP demonstrate the presence of beta -adrenergic receptors at a density of 83 fmol/mg membrane protein. Assessment of the effects of the beta(1)-specific antagonist CGP 20712A on [(125)I]ICYP binding and on isoproterenol (ISO)-sensitive adenylyl cyclase activity indicates that 67% of the receptors are beta(1)and 33% are beta(2), compared to 16-20%beta(2)in rat myocytes. Mouse myocytes respond to isoproterenol to produce cyclic AMP with an EC(50) approximately 110+/-20 n M. A functional G(i)pathway is demonstrated by inhibition of ISO-stimulated cyclic AMP accumulation by endothelin, carbachol and ATP and by sensitivity of this inhibition to pertussis toxin. As assessed by inositol phosphate production, endothelin and ATP stimulate the activity of the G(q)-phospholipase C pathway, whereas carbachol, PGF(2 alpha)and alpha(1)-adrenergic receptor agonists show no significant effect. The inability of alpha(1)-adrenergic receptor agonists to induce phosphoinositide hydrolysis in mouse myocytes differs from a several fold alpha(1)-adrenergic activation that occurs in rat. Biochemical and pharmacological profiles, as well as the need for modifications in experimental design, indicate that mouse myocytes differ substantially from rat cardiac myocytes.
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PMID:Characterization of G-protein signaling in ventricular myocytes from the adult mouse heart: differences from the rat. 1086 Jul 64

F(2)-Isoprostanes are generated from a cyclooxygenase-independent oxidative modification of arachidonic acid. They are present in atherosclerotic plaques and are platelet activators as well as potent vasoconstrictors. Polymorphonuclear neutrophils are major players in ischemia/reperfusion injury and in restenosis after PTCA. The effects of 8-isoprostaglandin (PG) F(2alpha) on very rapid beta(2)-integrin-dependent adhesion was evaluated in human neutrophils in vitro by use of purified integrin as ligand. 8-Iso-PGF(2alpha) (1 nmol/L to 20 micromol/L) triggers a dose-dependent, very rapid neutrophil adhesion to human fibrinogen but not to the endothelial ligand intercellular adhesion molecule-1. Pretreatment with anti-ss(2)-integrin subtypes showed activation of CD11b/CD18 and CD11c/CD18. Adhesion triggering was completely prevented by pertussis toxin. SQ29,548, a specific antagonist of thromboxane A2 receptor, also dose-dependently prevented 8-iso-PGF(2alpha)-triggered neutrophil adhesion. 8-Iso-PGF(2alpha) did not trigger adhesion in human monocytes and lymphocytes and did not induce neutrophil chemotaxis or activation of the oxygen free-radical-forming enzyme NADPH-oxidase. These data highlight the role of 8-iso-PGF(2alpha) as a specific activator of rapid neutrophil adhesion and suggest its involvement in the pathogenesis of ischemia/reperfusion injury and in restenosis after PTCA. The effect is transduced via activation of the receptor for thromboxane A2.
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PMID:8-Iso-PGF2 alpha induces beta 2-integrin-mediated rapid adhesion of human polymorphonuclear neutrophils: a link between oxidative stress and ischemia/reperfusion injury. 1114 33

In the ovary it has been demonstrated that PGF(2alpha) activates the phospholipase C (PLC)/diacylglycerol/protein kinase C pathway. However, little is known about the downstream signaling events that mediate subsequent cellular responses such as steroidogenesis. The present study was designed to examine the effect of PGF(2alpha) on activation of the mitogen-activated protein kinase (MAPK) signaling pathway and its physiological role in human granulosa-luteal cells (hGLCs). Human GLCs, obtained from women undergoing in vitro fertilization-embryo transfer, were treated with increasing concentrations of PGF(2alpha) (10 nmol/L to 10 micromol/L) for 5 min. For time-course experiments, hGLCs were treated with 1 micromol/L PGF(2alpha) for 1, 5, 10, or 20 min. Western blot analysis, using a monoclonal antibody that detected the phosphorylated forms of extracellular signal-regulated kinases 1 and 2 (p42(mapk) and p44(mapk), respectively), demonstrated that PGF(2alpha) activated MAPK in hGLCs in a dose- and time-dependent manner. Treatment of the cells with neomycin (10 mmol/L; a PLC inhibitor), bisindolylmaleimide I (5 micromol/L; a PKC inhibitor), or PD98059 (50 micromol/L; a MEK inhibitor and a MAPK kinase inhibitor) significantly attenuated the PGF(2alpha)-induced activation of MAPK. In contrast, MAPK activation was not significantly affected by pertussis toxin (200 ng/mL; a G(i) inhibitor) pretreatment. To determine the role of MAPK in steroidogenesis, hGLCs were treated with PGF(2alpha) (1 micromol/L), hCG (1 IU/mL), or PGF(2alpha) plus hCG in the presence or absence of PD98059. Progesterone levels in the culture medium were examined by RIA. Treatment of hGLCs with PGF(2alpha) significantly inhibited hCG-induced progesterone production. The presence of the MEK inhibitor, PD98059, reversed the inhibitory effect of PGF(2alpha) on hCG-induced progesterone production. To our knowledge, it is the first demonstration of PGF(2alpha)-induced activation of the MAPK signaling pathway in the human ovary. These results indicated that PGF(2alpha) activated MAPK subsequent to PLC and PKC activation through pertussis toxin-insensitive G protein in hGLCs. Further, we demonstrated that PGF(2alpha)-induced MAPK activation is associated with modulation of progesterone production. These results support the idea that the MAPK signaling pathway is involved in mediating PGF(2alpha) actions in the human ovary.
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PMID:Role of mitogen-activated protein kinase in prostaglandin f(2alpha) action in human granulosa-luteal cells. 1123 27

Prostaglandin (PG) F(2alpha) may act on its G protein-coupled receptor (FP) or be imported intracellularly via a transporter, which has high affinity for PGF(2alpha) and PGE(2), but not prostacyclin (PGI(2)). In cells overexpressing the epitope-tagged FP together with the human prostaglandin transporter (hPGT), stimulation of the FP with PGF(2alpha) (1 nM-1 microM), or the less potent FP agonist, the isoprostane 8,12-iso-iPF(2alpha)-III, inhibited prostaglandin uptake via the hPGT. This effect was abolished by pretreatment of the cells with cholera toxin, but not with pertussis toxin. Furthermore, two dominant negative constructs directed against Galpha(s) partially blocked FP-mediated regulation of hPGT function, also suggesting Galpha(s) involvement in this phenomenon. Surprisingly, neither an activator (dibutyryl cyclic AMP) nor an inhibitor (H89) of cyclic AMP-dependent protein kinase had any effect on FP-mediated inhibition of hPGT activity. Furthermore, although PGF(2alpha) increases intracellular cyclic AMP via Galpha(s) activation, it does not induce phosphorylation of the transporter, excluding a role of cyclic AMP-dependent protein kinase in hPGT regulation. Activation of the PGI(2) receptor, which is also coupled to Galpha(s), does not regulate hPGT activity, despite markedly augmenting adenylate cyclase activation. In conclusion, activation of the FP reduces intracellular import of prostaglandins for metabolic inactivation, increasing prostanoid availability for membrane receptor activation. This effect seems to be mediated via Galpha(s), independent of adenylate cyclase and cyclic AMP-dependent protein kinase activation.
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PMID:Prostaglandin F(2alpha) receptor-dependent regulation of prostaglandin transport. 1135 12

Oxytocin stimulates a rapid increase in ovine endometrial prostaglandin (PG) F2alpha synthesis. The overall objective of these experiments was to investigate the cellular mechanisms by which oxytocin induces endometrial PGF2alpha synthesis. The objective of experiment 1 was to determine whether G(i) proteins mediate oxytocin-induced PGF2alpha synthesis. Uteri were collected from four ovary-intact ewes on Day 14 postestrus. Caruncular endometrial explants were dissected and subjected to in vitro incubation. Pertussis toxin, an inhibitor of G(i) proteins, had no effect on the ability of oxytocin to induce PGF2alpha synthesis (P > 0.10). The objective of experiment 2 was to determine whether any of the three mitogen-activated protein kinases (MAPKs), extracellular signal regulated protein kinase (ERK1/2), c-Jun N-terminal/stress-activated protein kinase (JNK/SAPK), or p38 MAPK, mediate oxytocin-induced PGF(2alpha) synthesis. Eleven ovary-intact ewes were given an injection of oxytocin (10 IU; i.v.; n = 5) or physiological saline (i.v.; n = 6) on Day 15 postestrus. Uteri were collected 15 min after injection and caruncular endometrium was dissected. Endometrial homogenates were prepared and subjected to Western blotting. Membranes were probed for both total and phosphorylated forms of all three classes of MAPK. All classes of MAPK were detected in ovine endometrium, but oxytocin treatment had no effect on the expression of these proteins (P > 0.10). ERK1/2 was the only phosphorylated MAPK detected and its concentrations were higher in oxytocin-treated ewes (P < 0.01). The objective of experiment 3 was to further investigate the role of ERK1/2 during oxytocin-induced PGF2alpha synthesis. Uteri were collected from four ovary-intact ewes on Day 14 postestrus. Caruncular endometrial explants were dissected and subjected to in vitro incubation. PD98059, a specific inhibitor of ERK1/2 activity, blocked the ability of oxytocin to stimulate PGF(2alpha synthesis in a dose-dependent manner (P < 0.05). These results indicate that the ovine oxytocin receptor is not coupled to G(i) proteins. These results indicate that oxytocin induces phosphorylation of ERK1/2 and that this MAPK appears to mediate oxytocin-induced PGF2alpha synthesis in ovine endometrium.
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PMID:Cellular mechanisms by which oxytocin mediates ovine endometrial prostaglandin F2alpha synthesis: role of G(i) proteins and mitogen-activated protein kinases. 1156 37

1. The mouse AtT-20/D16-16 anterior pituitary tumour cell line was used as a model system for the study of the effects of prostaglandins upon the late stages of the adrenocorticotrophin (ACTH) secretory pathway. 2. Calcium (1 nM - 100 microM), guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S) (1 - 100 microM) and mastoparan (1 and 10 microM) all stimulated ACTH secretion from permeabilized AtT-20 cells in a concentration-dependent manner. GTP-gamma-S and mastoparan stimulated ACTH secretion from permeabilized cells in the absence of calcium. Co-incubation with prostaglandins E(1) and E(2) (PGE(1), PGE(2)) (10 microM) but not prostaglandin F(2 alpha) (PGF(2 alpha)) (10 microM) significantly inhibited calcium-, GTP-gamma-S and mastoparan-evoked secretion by 30 - 50%. 3. The effects of PGE(1) and PGE(2) upon GTP-gamma-S (100 microM)-, calcium (10 microM)- and mastoparan (10 microM)-evoked secretion were concentration-dependent. PGE(1) significantly inhibited GTP-gamma-S- and calcium-evoked secretion at concentrations of PGE(1) above 1 microM but mastoparan-evoked secretion only at the highest concentration of PGE(1) investigated (10 microM). PGE(2) was much more potent than PGE(1) and significantly inhibited GTP-gamma-S- and calcium-evoked secretion at 10 nM and above and mastoparan-evoked secretion above 1 microM. 4. The inhibitory effects of PGE(1) and PGE(2) upon calcium-, GTP-gamma-S- and mastoparan-stimulated ACTH secretion from permeabilized cells were pertussis toxin (PTX) sensitive. 5. In intact cells PGE(1), PGE(2) and PGF(2 alpha) (1 nM - 10 microM) acting singly had little or no effect upon ACTH secretion. However, only PGE(2) (1 nM - 10 microM) significantly inhibited corticotrophin-releasing factor-41 (CRF-41) (100 nM)-evoked secretion in a concentration dependent manner. 6. The present study finds that prostaglandins of the E series exert an inhibitory action, via a pertussis toxin-sensitive GTP-binding (G)-protein, in the late stages of the ACTH secretory pathway distal to the G-exocytosis (Ge)/calcium point of control.
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PMID:A direct inhibitory action of prostaglandins upon ACTH secretion at the late stages of the secretory pathway of AtT-20 cells. 1195 87

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