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 regulation of Cl- channels in human myoballs by G proteins was studied using whole-cell and inside-out patch recordings. After perfusion of the cell with 0.1 mM GTP[gamma S], the specific Cl- conductance, GCl, at standard resting potential (-85 mV) was increased from 5.9 microS/cm2 to 103 microS/cm2, and the kinetics upon stepping the potential to positive values was changed from an activating current with very slow inactivation to a fast inactivating current with no potential-dependent activation. These effects were not affected by the simultaneous blockade of several signal cascades involving G proteins. Addition of the protein kinase blockers PKI (25 microM), H8 (10 microM), or of the phospholipase-A2-blocking agent quinacrine (10 microM), had not much influence on these GTP[gamma S] effects. Buffering of the intracellular Ca2+ concentration (0.1 microM) or addition of the Ca2+/calmodulin antagonist trifluoperazine (50 microM) was also without effect. Pre-incubation of the cells with pertussis toxin or with cholera toxin did not change GCl. In excised inside-out patches voltage-clamped at -85 mV, application of GTP[gamma S] influenced the "intermediate" Cl- channel, the Cl- channel type having the highest density in these cells, by increasing the number of transitions in a half-conductance state. The probability of the channel being in one of the two conducting states rose from 0.015 to 0.67, and the kinetics of the single-channel currents was changed so that, on average, it was similar to the whole-cell current kinetics seen after application of GTP[gamma S]. It is concluded that a G protein is directly interacting with these channels.
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PMID:Chloride channels in cultured human skeletal muscle are regulated by G proteins. 127 15

Prenalterol, an allegedly beta 1-selective adrenergic agonist with high intrinsic sympathomimetic activity (ISA), was shown to be weakly lipolytic in rat adipocytes. However, in pertussis-toxin-treated adipocytes, the ISA of prenalterol was markedly increased (from 10-20% to approx. 100% of that of isoprenaline). The cellular sensitivity was also increased (EC50 approx. 60 nM and approx. 3 microM in pertussis-toxin-treated and control cells respectively). A similar effect was seen for other partial agonists such as the beta 2-selective agonist terbutaline and for beta-adrenergic antagonists with some intrinsic activity (metoprolol, pindolol). There was no clear change in sensitivity to isoprenaline's ability to stimulate adenylate cyclase in adipocyte membranes from pertussis-toxin-treated animals but the cyclase activity was increased approx. 4-fold in the presence of 1 microM-GTP. Prenalterol stimulated lipolysis by only small increases in intracellular cyclic AMP (cAMP) levels (less than 10% of that seen with isoprenaline). Basal lipolysis was increased in cells from pertussis-toxin-treated rats and the cellular sensitivity to the non-degradable cAMP analogue, N6-monobutyryl-cAMP, was increased. In control cells, a submaximal concentration of prenalterol (0.1 microM) increased the sensitivity to the cAMP analogues, N6-monobutyryl-cAMP and 8-bromo-cAMP. A low concentration (1 mM) of 8-bromo-cAMP also increased the effect of prenalterol. Similar effects were seen when the phosphodiesterase was inhibited. Thus (1) lipolysis is extremely sensitive to small increases in intracellular cAMP; (2) the degree of activation of adenylate cyclase and thus cAMP formation is the rate-limiting step for the biological response of partial agonists; (3) the inhibitory GTP-binding protein, Gi, is an important modulator ('tissue factor') of the beta-adrenergic agonistic property; (4) low levels of cAMP exert a priming effect on protein kinase A.
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PMID:The inhibitory GTP-binding protein (Gi) regulates the agonistic property of beta-adrenergic ligands in isolated rat adipocytes. Evidence for a priming effect of cyclic AMP. 128 Jan 15

5-hydroxytryptamine (5-HT) is a mitogen for fibroblasts, vascular smooth muscle cells, renal mesangial cells, and jejunal crypt cells. The human carcinoid cell line (termed BON) that we established in our laboratory from a pancreatic carcinoid tumor produces and secretes 5-HT. In this study, therefore, we examined the effect of 5-HT on growth of BON cells. Furthermore, by use of selective 5-HT receptor antagonists, we examined receptor and post-receptor mechanisms by which 5-HT-induced responses were produced. 5-HT stimulated growth of BON cells. 5-HT stimulated phosphatidylinositol (PI) hydrolysis in a dose-dependent fashion and inhibited cyclic AMP production in a dose-dependent fashion. The 5-HT1A/1B receptor antagonist, SDZ 21-009, prevented the reduction of cyclic AMP production evoked by 5-HT and inhibited the mitogenic action of 5-HT. The 5-HT1C/2 receptor antagonist, mesulergine, competitively inhibited PI hydrolysis, but did not affect the mitogenic action of 5-HT. The mitogenic action of 5-HT and the reduction of cyclic AMP production evoked by 5-HT were also inhibited by pertussis toxin. These results suggest that 5-HT is an autocrine growth factor for BON cells and that mitogenic mechanism of 5-HT involves receptor-mediated inhibition of the production of cyclic AMP which may be linked to pertussis toxin-sensitive GTP binding protein. 8-bromo-cyclic AMP inhibited growth of BON cells whereas 8-bromo-cyclic GMP had no effect on cell growth. Involvement of protein kinase A in BON cell growth regulation was confirmed by the observation that a cAMP-dependent protein kinase antagonist (Rp-cAMPS) could stimulate BON cell growth.
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PMID:Receptor-mediated autocrine growth-stimulatory effect of 5-hydroxytryptamine on cultured human pancreatic carcinoid cells. 130 21

The mechanism of adenylyl cyclase desensitization by carbachol, an agent that stimulates polyphosphoinositide hydrolysis, was studied in thyroid cells. Incubation of cultured dog thyroid cells with 10 microM carbachol for 2-4 hr reduced the subsequent thyrotropic hormone (TSH) stimulation of adenylyl cyclase activity of membrane preparations by approximately 40%. This inhibition was reversed by atropine, occurred even in a Ca(2+)-free medium containing ethylene glycol bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid, and was not reproduced by the Ca2+ ionophore A23187. The carbachol effect was not prevented by simultaneous incubation of cells with either isobutylmethylxanthine, an inhibitor of phosphodiesterase, or H-7, an inhibitor of protein kinase. Pretreatment of cells with pertussis toxin to inactivate the Gi inhibitory protein also failed to affect the carbachol inhibition. Although carbachol did not reduce the basal or the TSH-stimulated cyclase activities when added to membranes directly during the assay, exposure of cells to carbachol for 2-4 hr resulted in long lasting inhibition of TSH-stimulated cyclase activity (for at least 24 hr); recovery was seen by 48 hr after its removal. Carbachol pretreatment had no effect on 125I-TSH binding to membranes but reduced the cyclase stimulation by not only TSH but also cholera toxin, guanosine 5'-O-(3-thio)triphosphate, and forskolin; it also significantly reduced the cholera toxin-mediated AD[32P]-ribosylation of Gs in membranes. These data indicate that carbachol-induced inhibition of adenylyl cyclase occurs beyond the level of TSH receptor binding and that Gs is a possible site of its action. Thus, in dog thyroid cells, carbachol, via muscarinic receptors, can reduce the adenylyl cyclase activity by a process that does not involve Ca2+ or activation of phosphodiesterase.
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PMID:Carbachol-induced decrease in thyroid cell adenylyl cyclase activity is independent of calcium and phosphodiesterase activation. 131 Jan 40

The activation of adenosine A1 receptors in DDT1-MF2 smooth muscle cells resulted in both the inhibition of agonist-stimulated cAMP accumulation and the potentiation of norepinephrine-stimulated phosphoinositide hydrolysis. Pharmacological analysis indicated the involvement of an A1 adenosine receptor subtype in both of these responses. In the absence of norepinephrine, the activation of the adenosine receptor did not directly stimulate phosphoinositide hydrolysis. The adenosine receptor-mediated augmentation of norepinephrine-stimulated phosphoinositide hydrolysis was pertussis toxin sensitive and was selectively antagonized by agents that mimicked cAMP (8-bromo-cAMP) or raised cellular cAMP levels (forskolin). This initially suggested that cAMP might partially regulate the magnitude of the phospholipase C response to norepinephrine and that adenosine agonists might enhance the phospholipase C response by reducing cAMP levels. However, neither the reduction of cellular cAMP levels by other agents nor the inhibition of cAMP-dependent protein kinase was sufficient to replicate the action of adenosine receptor activation on phosphoinositide hydrolysis. Thus, in the presence of norepinephrine, adenosine receptor agonists appear to stimulate phosphoinositide hydrolysis via a pathway that is separate from, but dependent upon, that of norepinephrine. This second pathway can be distinguished from that which is stimulated by norepinephrine on the basis of its sensitivity to inhibition by both cAMP and pertussis toxin.
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PMID:Cyclic AMP differentiates two separate but interacting pathways of phosphoinositide hydrolysis in the DDT1-MF2 smooth muscle cell line. 131 18

The effect of endothelin-1 (ET-1) on differentiation of rat adipocyte precursor cells in serum-free culture and of the adipogenic fibroblast cell line TA1 was studied. ET-1 inhibited differentiation of rat adipocyte precursor cells into adipocytes in a dose-dependent fashion, while the peptide exerted no effect on TA1 cells. Rat adipose precursor cells possessed a single class of high affinity ET-1 receptor with a Kd of 0.71 nM and a binding capacity of 47,000 sites/cell. Affinity cross-linking of [125I]ET-1 showed two bands with molecular masses of 86 and 50 kilodaltons in rat adipose precursor cells and a single broad band with a molecular mass of 55-60 kilodaltons in TA1 cells. Pertussis toxin and the protein kinase-C inhibitors, H-7 and staurosporine, all of which enhanced adipocyte differentiation of rat adipose precursor cells, partially reversed ET-1 inhibition. These results showed the divergent effect of ET-1 on adipocyte conversion and indicated the possible involvement of a pertussis toxin-sensitive pathway and protein kinase-C at least in part in the inhibitory action of ET-1 on adipocyte differentiation.
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PMID:Endothelin-1 suppression of rat adipocyte precursor cell differentiation in serum-free culture. 131 37

Adenylyl cyclase in rat adipose cells is stimulated by ligands for Rs receptors (e.g. isoproterenol) and inhibited by ligands for Ri receptors (e.g. adenosine). In contrast, Rs receptors mediate inhibition and Ri receptors mediate augmentation of insulin-stimulated glucose transport activity by a process independent of changes in cellular cAMP-dependent protein kinase activity [Kuroda M., Honnor R. C., Cushman S. W., Londos C. and Simpson I. A. (1987) J. biol. Chem. 262, 245-253]. The present study examines the possible role of G-proteins in the regulation of insulin-stimulated glucose transport activity by Rs and Ri receptors. First, conditions were established that permit intoxication of isolated rat adipocytes by cholera and pertussis toxins without compromising cell integrity. Effectiveness of toxin treatment was monitored by examining adenylyl cyclase activity in isolated plasma membranes. Secondly, neither toxin interfered with the ability of a maximal concentration insulin to initiate the glucose transport response. Thirdly, pertussis toxin eliminated the augmenting effects of adenosine on insulin-stimulated glucose transport activity, but enhanced the inhibitory effects of isoproterenol. Findings with ligands for other Ri receptors (nicotinic acid and prostaglandin E2) mirrored those with adenosine. Finally, cholera toxin elicited a modest depression of transport activity, and only in the absence of an Ri ligand (e.g. adenosine). Furthermore, in contrast to the enhanced stimulation of adenylyl cyclase by isoproterenol and GTP, cholera toxin eliminated the inhibitory effect of isoproterenol on transport activity. The augmentative effects of adenosine on transport activity were unchanged. Measurements of (-/+cAMP) cAMP-dependent protein kinase activity ratios reinforce the notion that modulation of glucose transport activity is independent of changes in cAMP. We conclude that regulation of glucose transport activity by Rs and Ri receptors is mediated by the G-proteins, Gs and Gi (or other toxin substrates), respectively. Inasmuch as such regulation occurs at the plasma membrane and appears to be cAMP-independent, it is suggested that glucose transporters may be direct targets for receptor: G-protein interactions.
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PMID:Cholera and pertussis toxins modify regulation of glucose transport activity in rat adipose cells: evidence for mediation of a cAMP-independent process by G-proteins. 131 47

Studies were performed to examine the regulation of atrial natriuretic peptide- (ANP) stimulated guanylate cyclase in the the inner medulla. Primary cultures of rat inner medullary collecting tubular cells exposed to 10(-7) M ANP increased cGMP formation to 31.2 +/- 1.8 compared to the basal production of 2.1 +/- 0.6 fm/micrograms protein. This response did not appear to be transduced via a Gi protein, as preincubation with pertussis toxin did not alter the response to 10(-7) M ANP, and saponized cells exposed to 10 microM GTP gamma S did not enhance the response to ANP (77.3 +/- 5.9 vs. 86.7 +/- 6.3 g/micrograms). Likewise, changes in extracellular Ca2+ from 0.5 to 3.0 mM, decrements in intracellular Ca2+ with EGTA or increments in intracellular Ca2+ with ionomycin (5 microM) did not significantly alter the response to ANP. Neither activation of protein kinase A with forskolin (36.5 +/- 5.1) nor of protein kinase C with s,n-1,2-dioctanoylglycerol (33.2 +/- 2.5) altered the response to 10(-7) M ANP (32.2 +/- 3.3, NS). As the inner medullary environment was hypertonic, the effect of altering tonicity was studied. Cells grown for 48 hours in hypertonic media (600 mOsm/kg H2O) displayed enhanced response to 10(-8) and 10(-7) M ANP when osmolality was raised by either Na+ alone or in combination with urea, but not by urea alone. Our studies demonstrate that ANP-stimulated guanylate cyclase is insensitive to alterations in either intra- or extracellular Ca2+, is not subject to inhibition by protein kinase, and does not involve a pertussis-sensitive G protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of atrial natriuretic peptide-stimulated cGMP production in the inner medulla. 131 78

Ca2+ and other polyvalent cations as well as polycations, such as neomycin, produce similar effects on intracellular second messengers and PTH release in dispersed bovine parathyroid cells, but it is unclear whether all of these agents share the same mechanism of action. The lectin Concanavalin-A (Con-A) and the activator of protein kinase-C tetradecanoylphorbol acetate (TPA) blunt the effects of elevated extracellular calcium (Ca2+) concentrations on several aspects of parathyroid function, including PTH release, the cytosolic calcium concentration, and the accumulation of cAMP and inositol phosphates. In the present studies we used these two agents as well as pertussis toxin as probes to investigate further whether neomycin acts on parathyroid cells through the same receptor-like mechanism used by extracellular Ca2+ to regulate parathyroid function. Con-A and TPA both enhanced PTH release by about 2-fold at 0.5-1 x 10(-4) M neomycin, concentrations that inhibited PTH release to an extent (40-50%) similar to that seen with high (1.5-2 mM) Ca2+. Con-A also reduced the inhibition of agonist-stimulated cAMP accumulation by the same concentrations of neomycin. Conversely, Con-A and TPA produced 70-80% decreases in the cytosolic calcium concentration transient and the accumulation of inositol phosphates stimulated by neomycin. The effects of these two agents on neomycin-regulated parathyroid function were similar in magnitude to their actions on the modulation of these same parameters by extracellular Ca2+. Pertussis toxin, however, which we have previously shown to block the inhibitory effects of high Ca2+ and neomycin on cAMP accumulation, had no effect on the inhibition of PTH release by these two agents. These results provide further indirect evidence that polyvalent cations and polycations act on the parathyroid cell through related pathways, which probably involve cell surface moieties containing carbohydrate(s).
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PMID:A comparison of the effects of concanavalin-A and tetradecanoylphorbol acetate on the modulation of parathyroid function by extracellular calcium and neomycin in dispersed bovine parathyroid cells. 131 77

A monoclonal antibody against GM3 ganglioside (GM3Ab) was found to trigger differentiation of Neuro-2a cells in culture. The differentiation of Neuro-2a cells by GM3Ab was accompanied by increased levels of intracellular serotonin and amino acid neurotransmitters viz. aspartate, glutamate, glutamine, glycine and taurine. Further study indicated that the increase in the serotonin level was not due to a higher rate of serotonin synthesis but rather to a higher rate of active transport of serotonin from the medium. Studies on the cell surface gangliosides revealed that unlike the proliferating cells, the GM3Ab-mediated differentiated cells contained higher gangliosides in addition to GM3 and GM2 gangliosides. Analysis of total cellular proteins indicated the appearance of a 25 kDa protein, pI 5.4, in the GM3Ab-treated cells--a small amount of this protein was observed in dibutyryl cAMP (Bt2cAMP)-treated cells, however, the protein was totally absent in the 5-bromo-2'-deoxyuridine (BrdU)-treated cells. Investigation of the mode of action of GM3Ab indicated that the cellular differentiation was due to increased cAMP accumulation resulting from an increase in the adenylate cyclase activity. Further studies with different agents affecting protein kinase C (PKC) activity and direct assay of PKC ruled out the possibility that GM3Ab mediated its effect via PKC. This GM3Ab-induced differentiation could be inhibited by protein kinase A (PKA) inhibitor, H8, but could not be inhibited by sphingosine, an inhibitor of PKC. Pertussis toxin could mimic the effect of GM3Ab, suggesting that GM3Ab caused the elevation in the adenylate cyclase activity by reducing the Gi-protein inhibition of the adenylate cyclase. The data suggests that GM3Ab, after interaction with cell surface GM3, elevated intracellular cAMP level by withdrawing the inhibitory effect of some undefined factor(s) present in culture medium which normally keeps adenylate cyclase activity low through activation of Gi-protein.
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PMID:Differentiation of Neuro-2a neuroblastoma cells by an antibody to GM3 ganglioside. 132 94

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