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)

Rat osteosarcoma 17/2.8 cells (Ros 17/2.8 cells) were labeled with [32P]PO4(2-), and their levels of inositol lipids were determined after stimulation with thrombin. Thrombin stimulated a pertussis toxin-sensitive rapid accumulation of phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4,5)P3] with lesser increases in levels of phosphatidylinositol-3,4-bisphosphate [PtdIns(3,4)P2] and phosphatidylinositol-3-phosphate [PtdIns3P] that were slower in onset. Ros 17/2.8 cell homogenates contained phosphatase activities that hydrolyzed PtdIns(3,4,5)P3 to PtdIns(3,4)P2 and PtdIns3P. Phosphoinositide-3-kinase activity was determined in Ros 17/2.8 cell homogenates using exogenously provided PtdIns(4,5)P2. Guanosine-5'-3-O-(thio)triphosphate caused an approximately 3-fold increase in phosphoinositide-3-kinase activity in a manner that was blocked by high concentrations of guanosine-5'-2-O-(thio)diphosphate. Purified bovine brain G protein beta gamma subunits also increased phosphoinositide-3-kinase activity modestly in Ros 17/2.8 cell homogenates. Ros 17/2.8 cell homogenates contained phosphatase activities that sequentially dephosphorylated PtdIns(3,4,5)P3 to PtdIns(3,4)P2 and PtdIns3P. Two peaks of phosphoinositide-3-kinase activity were resolved by anion exchange chromatography of a Ros 17/2.8 cell cytosolic extract. The later elution of these was selectively activated by beta gamma subunits (16-fold activation with 16 microM beta gamma subunits). Half-maximal effects of the beta gamma subunits were observed at a concentration of 0.6 microM, and activation was blocked by preincubation of the beta gamma subunits with an excess of recombinant Gi alpha 2. beta gamma Subunits did not activate the p85 alpha/p110 beta form of phosphoinositide-3-kinase purified from sf9 cells after expression with the use of baculovirus vectors.
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PMID:Regulation of phosphoinositide-3-kinase by G protein beta gamma subunits in a rat osteosarcoma cell line. 756 35

D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] inhibits human red blood cell (RBC) Ca(2+)-stimulable, Mg(2+)-dependent adenosine triphosphatase (Ca(2+)-ATPase) activity in vitro. Because we have previously shown that adrenergic receptors exist on the human mature RBC membrane and can modulate Ca(2+)-ATPase activity, we examined the possibility that a guanine nucleotide regulatory protein (G protein) mediated the Ins(1,4,5)P3 effect. Guanosine 5'-O-(3-thiotrisphosphate) (GTP gamma S) 10(-4) mol/L also inhibited RBC Ca(2+)-ATPase activity. Pertussis toxin 200 ng/mL blocked the effects of both Ins(1,4,5)P3 and GTP gamma S on Ca(2+)-ATPase activity. In separate studies, pertussis toxin-catalyzed adenosine diphosphate (ADP) ribosylation was shown to occur in RBC membranes under conditions in which measurements of Ca(2+)-ATPase activity were performed. When Ins(1,4,5)P3 10(-7) mol/L and GTP gamma S 10(-6) mol/L were added to membranes concurrently, their inhibitory actions on the enzyme were additive. At greater concentrations of Ins(1,4,5)P3 (10(-6) to 10(-5) mol/L) and GTP gamma S (10(-4) mol/L), the inositol phosphate reversed the inhibitory effect of GTP gamma S. These observations indicate that the novel effect of Ins(1,4,5)P3 on the activity of a plasma membrane Ca(2+)-ATPase depends at least in part on the action of a pertussis toxin-susceptible G protein.
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PMID:Inositol phosphates modulate human red blood cell Ca(2+)-adenosine triphosphatase activity in vitro by a guanine nucleotide regulatory protein. 761 44

The steroid hormone 1,25(OH)2-vitamin D-3 [1,25(OH)2D3] stimulated phospholipase A2 (PLA2) activity in embryonic chick myoblasts releasing [3H]arachidonic acid from the sn-2 position of phospholipids. GTP-binding protein mediation of 1,25(OH)2D3-dependent PLA2 activity was investigated in cells prelabeled with [3H]arachidonic acid. AIF4-, a G-protein activator, mimicked 1,25(OH)2D3-stimulated arachidonic acid release from myoblasts in a dose-dependent manner. Consistent with the involvement of a G-protein in the activation of PLA2 by the hormone, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), a stable GTP analogue which activates G-protein mediated signals, strongly enhanced arachidonic acid release in myoblasts. Guanosine 5'-O-(2-thiodiphosphate) (GDP beta S), which competitively inhibits G-protein activation by GTP and its analogues, abolished 1,25(OH)2D3-dependent arachidonic acid release. Bordetella pertussis toxin pretreatment significantly suppressed the hormone action whereas cholera toxin had minor effects on 1,25(OH)2D3 action. Hormone-induced activation of PLA2 was mimicked by the Ca2+ ionophore A23187 and blocked by nifedipine, but was unaffected by neomycin, a phospholipase C inhibitor, ruling out the contribution of phosphoinositide metabolism to arachidonic acid release. These results suggest that 1,25(OH)2D3-stimulation of PLA2 activity in embryonic chick myoblasts is mediated by a pertussis toxin-sensitive GTP-binding protein coupled to influx of extracellular calcium.
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PMID:1,25(OH)2-vitamin D-3 stimulates phospholipase A2 activity via a guanine nucleotide-binding protein in chick myoblasts. 764 3

Guanosine 5'-[beta gamma-imido]triphosphate (p[NH]ppG)-stimulated phospholipase C (PLC) activity in bovine brain coated vesicles is inhibited by glutamate agonists. In the present study we show that quisqualic acid (QA), (+/-)-trans-1-aminocyclopentane-1,3-dicarboxylate (trans-ACPD), glutamic acid and ibotenic acid inhibited p[NH]ppG-stimulated PLC by 44, 41, 36 and 25% respectively. Carbachol also produced an inhibition of p[NH]ppG-stimulated PLC by 45%. The inhibition caused by trans-ACPD and QA was dose-dependent. DL-2-Amino-3-phosphonopropionic acid and (RS)-alpha-methyl-4-carboxyphenylglycine, specific antagonists of metabotropic glutamate receptors (mGluRs), abolished these inhibitory effects. trans-ACPD inhibition of p[NH]ppG-stimulated PLC was also observed in the presence of ionotropic glutamate receptor antagonists. When carbachol and QA or trans-ACPD were combined, additive inhibitory effects were observed. Preincubation of bovine brain coated vesicles with pertussis toxin abolished the inhibitory effects of mGluR analogues and carbachol on p[NH]ppG-stimulated PLC activity. The presence of Gs alpha and pertussis toxin substrates, Gi alpha and Go alpha subunits as well as PLC beta 1 in bovine brain coated vesicles has been confirmed by immunoblot. These results support the coupling of mGluRs to a PLC in an inhibitory manner through a pertussis toxin-sensitive G-protein in bovine brain coated vesicles.
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PMID:Metabotropic glutamate receptor analogues inhibit p[NH]ppG-stimulated phospholipase C activity in bovine brain coated vesicles: involvement of a pertussis toxin-sensitive G-protein. 774 17

The alpha adrenergic agonist phenylephrine increases the long-lasting Ca++ channel current (L-type Ca++ channel current) in neonatal rat ventricular cells. In these experiments, the intracellular mechanism of the alpha (alpha-1A) adrenergic effect was investigated. Guanosine-5'-O-(2-thiodiphosphate), a G-protein inhibitor, blocked and guanosine-5'-O-(3-thiotriphosphate), a G-protein activator, mimicked the effect of phenylephrine, suggesting that G-proteins are involved in the activation of the alpha-1 adrenoceptor-induced increase in Ca++ channel current. The effect of phenylephrine on the L-type current was not abolished in cells pretreated with pertussis toxin and cholera toxin, indicating that pertussis toxin- and cholera toxin-insensitive G-proteins are coupled to the alpha-1A adrenoceptor. Acute treatment with 4 beta-phorbol-12-myristate and 1-oleoyl-2-acetyl-rac-glycerol, two protein kinase C activators, increased the L-type Ca++ channel current. Staurosporine and prolonged pretreatment with 4 beta-phorbol-12-myristate blocked the effect of phenylephrine. This suggests that protein kinase C activation is involved in the mechanism. The results described in this study suggest that stimulation of the alpha-1A adrenoceptor results in the activation of pertussis toxin- and cholera toxin-insensitive G-proteins which may lead to phosphorylation of Ca++ channel proteins through protein kinase C. The phosphorylation of channel protein results in an increase in the L-type Ca++ channel current in neonatal rat ventricular cells.
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PMID:L-channel modulation by alpha-1 adrenoceptor activation in neonatal rat ventricular cells: intracellular mechanisms. 796 16

Vascular smooth muscle cells (VSMC) from rat aorta possess specific receptors for a novel potent vasorelaxant peptide, adrenomedullin (AM). To elucidate its receptor coupling to guanine nucleotide-binding stimulatory protein and the structural requirement of the AM molecule to its vascular receptors, we have studied the effects of guanine nucleotides on [125I]human (h) AM binding and adenylate cyclase activity in cultured rat VSMC, and the effects of various synthetic hAM analogs on [125I]hAM binding and the cAMP response. Guanosine 5'-O-(3-thiotriphosphate) dose dependently inhibited [125I]hAM binding to rat VSMC membranes. hAM stimulated adenylate cyclase activity, and its effect was additive with GTP. hAM-induced cAMP formation was abrogated by pretreatment with cholera toxin, but not by that with pertussis toxin. Intact hAM-(1-52)-NH2 and N-terminal truncated derivatives [hAM-(13-52)-NH2, hAM-(16-52)-NH2] almost equally inhibited [125I]hAM binding and stimulated cAMP formation, whereas removal of C-terminal Tyr52 residue [hAM-(1-51)-NH2] remarkably decreased receptor-binding activity and the cAMP response. The effects of hAM-(1-52)-OH, hAM-(1-51)-OH, and a linear hAM analog ([carbamoylmethyl-Cys16,21]hAM-NH2) were far less potent on receptor binding and the cAMP response than that of hAM-(1-52)-NH2. The C-terminal fragment [hAM-(33-52)-NH2] and the N-terminal fragment [hAM-(1-10)-OH] had neither receptor-binding nor adenylate cyclase activity. hAM-(22-52)-NH2 had no agonistic effect, but showed an antagonistic effect on the hAM-induced cAMP response. These data suggest that vascular AM receptors are functionally coupled to adenylate cyclase via guanine nucleotide-binding stimulatory protein. Studies of the structure-activity relationship of hAM revealed that the cyclic structure formed by the disulfide bridge and amidation of the C-terminal residue of the AM molecule are critical for receptor binding and subsequent cAMP generation and suggest that the C-terminal fragment hAM-(22-52)-NH2 may be an antagonist for vascular AM receptors.
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PMID:Structure-activity relationship of adrenomedullin, a novel vasodilatory peptide, in cultured rat vascular smooth muscle cells. 798 31

GTP-binding protein (G-protein) regulation of inward rectifying K+ channels in the plasma membrane of Vicia (Vicia faba L.) guard cells has previously been demonstrated at the whole-cell level. However, whether a cytosolic signal transduction chain is required for G-protein regulation of K+ channels in Vicia guard cells, or in any plant cell type, remains unknown. In the present study, we assayed effects of several G-protein regulators on inward K+ channels in isolated inside-out membrane patches from Vicia guard cell protoplasts. Guanosine 5'-[gamma-thio]triphosphate, a nonhydrolyzable GTP analog that locks G proteins into their activated state, decreased the open state probability (Po) of single inward K+ channels. This decrease in Po was accompanied by an increase in one of the closed time constants of the K+ channel. Guanosine 5'-[beta-thio]diphosphate, a GDP analog that locks G proteins into their inactivated state, slightly increased the Po of the inward K+ channel and shortened the closed time constants. Pertussis toxin and cholera toxin, which ADP-ribosylate G proteins at different sites, decreased the Po of the inward K+ channel. Our data indicate that G proteins can act via a membrane-delimited pathway to regulate inward K+ channels in the guard-cell plasma membrane.
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PMID:A membrane-delimited pathway of G-protein regulation of the guard-cell inward K+ channel. 802 77

To investigate how G proteins regulate surfactant secretion, we subjected rat alveolar type II cells to conditions known to activate or to inactivate G proteins. AlF-4, which activates G proteins, inhibited secretion in intact cells. Guanosine-5'-O-(3-thiotriphosphate), which activates G proteins in permeabilized cells, stimulated secretion at basal cytosolic [Ca2+], but inhibited secretion at higher [Ca2+]. In contrast, guanosine-5'-O-(2-thiodiphosphate) (GDP beta S), which inactivates G proteins, stimulated secretion at each [Ca2+] tested. Because treatment with GDP beta S stimulated secretion at basal cytosolic [Ca2+], surfactant secretion appears to be subject to G protein-regulated tonic inhibition. Pertussis toxin (PTX) inhibited terbutaline- and ionomycin-stimulated secretion in intact cells, but did not inhibit secretion stimulated by either forskolin or 8-bromoadenosine 3',5'-cyclic monophosphate. Inhibition by PTX of terbutaline-stimulated, but not 8-bromoadenosine 3',5'-cyclic monophosphate- or forskolin-stimulated secretion, suggests that PTX-sensitive G proteins regulate beta-adrenergic-stimulated surfactant secretion proximal to second messenger generation. Inhibition of ionomycin-stimulated secretion, however, suggests that PTX-sensitive G proteins may also regulate non-receptor-mediated secretory events.
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PMID:Activation of G proteins may inhibit or stimulate surfactant secretion in rat alveolar type II cells. 817 14

The regulatory mechanism(s) of a phosphoinositide-specific phospholipase C, PLC-delta 1, was investigated using a clone of stably overexpressed PLC-delta 1 (PLC delta 30 cells) in Chinese hamster ovary cells. Thrombin stimulation of PLC delta 30 cells exhibited 6.5-fold increase in total inositol phosphates (InsP), which was significantly higher than that in the vector-transfected (V1) cells (2.0-fold). AIF-4 increased InsP accumulation in both V1 and PLC delta 30 cells, and pertussis toxin partially blocked InsP accumulation in thrombin-stimulated PLC delta 30 cells. Guanosine thiotriphosphate (GTP gamma S) markedly potentiated thrombin-stimulated InsP generation in permeabilized PLC delta 30 cells compared with V1 cells, suggesting possible involvement of a G-protein (s) in the activation of PLC-delta 1. In PLC delta 30 cells, ionomycin-induced significant InsP generation and thrombin-stimulated InsP generation were completely inhibited by addition of EGTA. Furthermore, the stimulatory effects of thrombin plus GTP gamma S in PLC delta 30 cells were more sensitive to change in free calcium concentration than in V1 cells. Suppression by 12-O-tetradecanoylphorbol 13-acetate of thrombin-stimulated InsP accumulation was not affected by increasing Ca2+ concentration. These results indicate that thrombin-induced PLC-delta 1 activation is regulated via both G-protein(s) and calcium.
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PMID:Thrombin-mediated phosphoinositide hydrolysis in Chinese hamster ovary cells overexpressing phospholipase C-delta 1. 819 39

Osteoclasts are the cells responsible for the resorption of bone and other mineralized tissues. GTP-binding proteins (G proteins) play important roles in regulating the activity of many cell types; however, there is limited knowledge of their functions in osteoclasts. We used the patch-clamp technique in the whole-cell configuration to introduce either hydrolysis-resistant guanosine triphosphate analogues or fluoroaluminate into single rat osteoclasts, and examined the effects of G protein activation on cell morphology and ionic conductances. Guanosine 5'-O-(3-thiotriphosphate) or 5'-guanylyl-imidodiphosphate, but not the control compounds adenosine 5'-O-(3-thiotriphosphate) or guanosine 5'-O-(2-thiodiphosphate), induced: (1) prompt spreading due to extension of lamellipodia; and (2) after a latency of several minutes, complete suppression of the inwardly rectifying K+ current. Pertussis toxin did not alter either spreading or suppression of K+ current induced by guanosine 5'-O-(3-thiotriphosphate). Cytochalasin D, but not colchicine, prevented guanosine 5'-O-(3-thiotriphosphate)-induced spreading, consistent with actin polymerization underlying lamellipod extension. Whole-cell capacitance did not change during guanosine 5'-O-(3-thiotriphosphate)-induced spreading, which is consistent with a lack of change in total plasma membrane area. Fluoroaluminate did not induce spreading, but it did suppress the K+ current. The differential effects of fluoroaluminate and guanosine 5'-O-(3-thiotriphosphate) suggest that lamellipod extension is regulated by a small molecular mass, monomeric G protein, whereas the inwardly rectifying K+ current is regulated by a large molecular mass, heterotrimeric G protein. Thus, osteoclast motility and ion transport are regulated by separate G protein-coupled pathways.
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PMID:Lamellipod extension and K+ current in osteoclasts are regulated by different types of G proteins. 820 76

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