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)

We have recently shown the selective inhibition of an amiloride-sensitive, conductive pathway for Na+ by atrial natriuretic peptide and 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) in the renal epithelial cell line, LLC-PK1. Using 22Na+ fluxes, we further investigated the modulation of Na+ transport by atrial natriuretic peptide and by agents that increase cGMP production, activate protein kinase c, or modulate guanine nucleotide regulatory protein function. Sodium nitroprusside increases intracellular cGMP concentrations without affecting cAMP concentrations and completely inhibits amiloride-sensitive Na+ uptake in a time- and concentration-dependent manner. In contrast, 8-BrcAMP is without effect on Na+ uptake through the Na+ channel. 1-Oleoyl 2-acetylglycerol (10 micrograms/ml) and phorbol 12-myristate 13-acetate (100 nM), activators of protein kinase c, inhibit Na+ uptake by 93 +/- 13 and 51 +/- 10%, respectively. Prolonged incubation with phorbol ester results in the downregulation of protein kinase c activity and reduces the inhibitory effect of atrial natriuretic peptide, suggesting that the action of this peptide involves stimulation of protein kinase c. Pertussis toxin, which induces the ADP-ribosylation of a 41-kDa guanine nucleotide regulatory protein in LLC-PK1 cells, inhibits 22Na+ influx to the same extent as amiloride. Thus, increasing cGMP, activating protein kinase c, and ADP-ribosylating a guanine nucleotide regulatory protein all inhibit Na+ uptake. These events may be sequentially involved in the action of atrial natriuretic peptide.
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PMID:Inhibition of epithelial Na+ transport by atriopeptin, protein kinase c, and pertussis toxin. 295 93

The cellular cGMP content increased in response to a variety of receptor agonists, which activate [e.g., prostaglandin (PG) E1, E2, and F2 alpha] or inhibit (e.g., alpha-adrenergic, muscarinic, and opiate agonists) adenylate cyclase in neuroblastoma X glioma hybrid NG108-15 cells. The responses were additive when PGF2 alpha and enkephalin were mixed. The inhibitory guanine nucleotide regulatory protein (Ni) is involved in adenylate cyclase inhibition; this function of Ni is lost when it is ADP-ribosylated by islet-activating protein (IAP), pertussis toxin [H. Kurose, T. Katada, T. Amano, and M. Ui (1983) J. Biol. Chem. 258, 4870-4875]. The cGMP rise induced by stimulation of the receptors linked to adenylate cyclase inhibition was also diminished by IAP; the time course and dose response for the IAP-induced diminution were the same between adenylate cyclase inhibition and cGMP generation. Ni thus appears to mediate guanylate cyclase activation as well as adenylate cyclase inhibition initiated via the same receptors. Melittin also increased cGMP. No additivity was shown when enkephalin and melittin were combined, suggesting that phospholipase A2 might play a role in Ni-mediated guanylate cyclase activation. On the other hand, the PGF2 alpha-induced cGMP rise was associated with increased incorporation of 32Pi into phosphatidylinositol; was not affected by cholera toxin, IAP or forskolin; and showed no additivity when combined with A23187, which increased cGMP by itself. PGs would occupy receptors linked to phosphatidylinositol breakdown, thereby increasing the availability of intracellular Ca2+, which is responsible for guanylate cyclase activation. Thus, dual pathways are proposed for a receptor-mediated cGMP rise in NG108-15 cells.
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PMID:Dual pathways of receptor-mediated cyclic GMP generation in NG108-15 cells as differentiated by susceptibility to islet-activating protein, pertussis toxin. 298 51

As noted previously, in N1E-115 neuroblastoma cells, carbamylcholine, a muscarinic cholinergic agonist, increased cGMP over 15-fold and decreased basal and prostaglandin E1 (PGE1)-stimulated cAMP content. In contrast to the stimulatory effects of PGE1 on cAMP, which were immediate, the carbamylcholine-induced decrease in basal and PGE1-stimulated cAMP exhibited a delay. The delay in carbamylcholine inhibition was independent of the extent of adenylate cyclase activation. Although basal cAMP content was suppressed within 30 sec after addition of carbamylcholine, inhibition was not maximal for at least 2 min following agonist addition; the delay was similar in cells exposed to PGE1 for 10 min prior to carbamylcholine but could be eliminated by incubation of the cells with muscarinic cholinergic agonist for 5 min prior to addition of prostaglandin. N1E-115 neuroblastoma cells possess a 41,000-Da membrane protein believed to be a component of the inhibitory GTP-binding protein of adenylate cyclase that is ADP ribosylated by pertussis toxin. Incubation of the cells with pertussis toxin prior to the addition of carbamylcholine reduced the maximal extent of inhibition of cAMP content and prevented the [32P]ADP-ribosylation of a 41,000-Da protein by toxin and [32P]NAD in membrane preparations from these cells. Incubation of cells with pertussis toxin, however, did not significantly alter the dose-response curve for carbamylcholine effects on cGMP. Even high concentrations of carbamylcholine, effective in stimulating cGMP, had minimal effects on cAMP content in toxin-treated cells; thus, ADP-ribosylation of Gi converts the adenylate cyclase but not the guanylate cyclase system to an agonist-insensitive state.
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PMID:Effects of pertussis toxin on cAMP and cGMP responses to carbamylcholine in N1E-115 neuroblastoma cells. 299 40

Experiments were carried out to investigate the influence of islet-activating protein (IAP), a pertussis toxin, on the autonomic regulation of cardiac function. In atria isolated from rats given intravenous IAP (0.125-1.0 micrograms/100 g body wt) 12-72 h prior to experiments, the negative chronotropic and inotropic actions of carbachol were attenuated in a dose- and time-dependent manner. The inhibitory action of carbachol in the absence of isoproterenol and its attenuation by IAP were not associated with any changes in tissue adenosine 3',5'-cyclic monophosphate (cAMP) levels. In addition, carbachol decreased the isoproterenol-induced elevation of cAMP levels and inhibited the positive chronotropic and inotropic responses to isoproterenol. The inhibitory action of carbachol on the isoproterenol-induced functional and cAMP responses was also reduced by the IAP treatment. The increase in tissue guanosine 3',5'-cyclic monophosphate (cGMP) levels produced by carbachol was likewise abolished by the IAP treatment. These results indicate that IAP treatment attenuates the inhibitory actions of carbachol elicited via muscarinic receptors through both cAMP-dependent and cAMP-independent subcellular processes.
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PMID:Attenuation of muscarinic cholinergic inhibition by islet-activating protein in the heart. 299 93

The tridecapeptide, neurotensin, inhibited prostaglandin E1-stimulated cyclic AMP production in intact plated neuroblastoma N1E115 cells. The peptide effect was concentration dependent (EC50 = 2 nM) and maximal inhibition reached 55% with 100 nM neurotensin. Acetyl neurotensin (8-13) was as active as neurotensin whereas neurotensins (1-8), (1-12), and (10-13) were barely active in inhibiting cyclic AMP production, thus showing the requirement of the carboxy terminal hexapeptide sequence of neurotensin for biological activity. The inhibitory effect of neurotensin on cyclic AMP production was largely prevented by pretreatment of N1E115 cells with islet-activating protein (pertussis toxin). In contrast, pertussis toxin did not inhibit neurotensin-stimulated cyclic GMP production in neuroblastoma cells. In cell membranes, the toxin promoted the selective ADP-ribosylation of a single protein having the same molecular weight (41,000) as the alpha-subunit of Ni, the inhibitory regulatory protein of adenylate cyclase. In membranes prepared from N1E115 cells, monoiodo[125I-Tyr3]neurotensin bound to a single population of receptors characterized, at 25 degrees and in the absence of monovalent cations and guanyl nucleotides, by a dissociation constant (Kd) of 56 pM and a maximal binding capacity (Bm) of 30 fmol/mg of protein. Na+ (10-100 mM) and GTP (0.1-100 microM) inhibited neurotensin binding in a concentration-dependent manner. At 100 mM Na+ and 100 microM GTP, receptor affinity was decreased by 5- and 2-fold, respectively. Li+ and K+ were less effective than Na+, and the effect of GTP was shared by GDP and guanyl-5'-yl-imidodiphosphate, but not by GMP, ATP, ADP, or adenyl-5'-yl-imidodiphosphate. It is concluded that in N1E115 cells, neurotensin attenuates cyclic AMP production by exerting an inhibitory effect on adenylate cyclase through an interaction of the peptide receptors with the regulatory GTP-binding protein Ni.
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PMID:Neurotensin-mediated inhibition of cyclic AMP formation in neuroblastoma N1E115 cells: involvement of the inhibitory GTP-binding component of adenylate cyclase. 301 77

Evidence is shown that protein kinase C is the major kinase which can phosphorylate histone H-1 in a membrane fraction prepared from rabbit peritoneal neutrophils. Addition of phorbol-12-myristate-13-acetate (PMA) (0.1 microgram/ml) or guanosine-5'-(3-O-thio)triphosphate (GTP gamma S) (10 microM) to the membrane fraction results in an increase of the phosphorylation of histone H-1. To achieve this effect, calcium (20 microM) is required for GTP gamma S but not for PMA. The effect of GTP gamma S, but not PMA is inhibited in membranes obtained from cells pretreated with pertussis toxin. The kinase activity is also enhanced by treatment of the membrane with 10 microM of GppNHp or GTP but not with GDP, GMP, cGMP, ATP, ADP, AMP and cAMP. This is the first direct evidence that a GTP binding protein is involved in the activation of membrane associated protein kinase C.
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PMID:Regulation of membrane associated protein kinase C activity by guanine nucleotide in rabbit peritoneal neutrophils. 302 4

The association of neurotensin to its receptor in differentiated neuroblastoma N1E115 cells led to a fast and transitory increase of the intracellular concentration in inositol triphosphate and inositol biphosphate, followed by a slower and more stable increase inositol monophosphate. The action of inositol 1,4,5-triphosphate on digitonin-permeabilized N1E115 cells resulted in a stimulation of cyclic GMP levels that mimicked that induced by neurotensin. Therefore, the cyclic GMP stimulation is probably a consequence of the initial inositol triphosphate formation triggered by neurotensin. Fluoroaluminate ions and pertussis toxin had the capacity to modulate positively and negatively, respectively, the formation of inositol triphosphate induced by neurotensin, indicating that GTP-binding proteins are involved in the regulation of inositol phosphate levels by neurotensin receptors.
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PMID:Stimulation of inositol phosphate production by neurotensin in neuroblastoma N1E115 cells: implication of GTP-binding proteins and relationship with the cyclic GMP response. 304 Sep 12

Information available at present documents the existence of three well-defined classes of guanine nucleotide binding proteins functioning as signal transducers: Gs and Gi which stimulate and inhibit adenylate cyclase, respectively, and transducin which transmits and amplifies the signal from light-activated rhodopsin to cGMP-dependent phosphodiesterase in ROS membranes. Go is a fourth member of this family. Its function is the least known among GTP binding signal transducing proteins. The family of G proteins has a number of properties in common. All are heterotrimers consisting of three subunits, alpha, beta, and gamma. Each of the subunits may be heterogeneous depending on species and tissue of origin and may be posttranslationally modified covalently. The alpha subunits vary in size from 39 to 52 kDa. The sequences for Gs alpha and transducin alpha have 42% overall homology and those of Gi alpha and Gs alpha 43%, whereas those of Gi alpha and transducin alpha have a higher degree (68%) of homology. All alpha subunits bind guanine nucleotides and are ADP-ribosylated by either pertussis toxin (Gi, transducin, Go) or cholera toxin (Gs, Gi, transducin). Thus, transducin and Gi, which have the highest degree of sequence homology, are also ADP-ribosylated by both toxins. The beta subunits have molecular weights of 36 and 35 kDa, respectively. While Gs, Gi, and Go contain a mixture of both, transducin contains only the larger (36-kDa) beta-polypeptide. The relationship of the 36- and the 35-kDa beta subunits is not defined. Although the complete sequence of the 36-kDa beta subunit of transducin has been deduced from the cDNA sequence, complete sequences of other beta subunits are not yet available so that detailed comparisons cannot be made at present. However, the proteolytic profiles of each class of the beta subunits of different G proteins are indistinguishable. The gamma subunit of bovine transducin has been completely sequenced. It has a Mr of 8400. Again complete sequences of other gamma subunits are not yet available. While the gamma subunits of Gs, Gi, and Go have identical electrophoretic mobility in SDS gels, they differ significantly in this respect from the gamma subunit of transducin. Moreover, crossover experiments point to functional differences between gamma subunits from G protein and transducin complexes. In addition, a role for beta, gamma in anchoring guanine nucleotide binding proteins to membranes has been postulated.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Structural and functional relationships of guanosine triphosphate binding proteins. 313 54

In the present study, we have characterized the effects of guanine nucleotides on agonist and antagonist binding to A1 adenosine receptors, which mediate inhibition of adenylate cyclase via the inhibitory G protein (Gi) in adipocytes. Our data indicate that guanosine-triphosphate (GTP) and guanyl-5'-yl imidodiphosphate (Gpp(NH)p) enhance the binding of 8-(4-[(([(2-amino-ethyl)amino]carbonyl) methyl)oxyl]phenyl)-1,3-dipropylxanthine ([3H]XAC) to adipocyte membranes in a dose-dependent manner, with EC50 values being 1.8 and 2.2 microM, respectively. The stimulatory effect of GTP was abolished in pertussis toxin-intoxicated membranes, implying a role of a pertussis toxin-sensitive G protein in mediating this effect. Furthermore, the ranked order of efficacy for a series of guanine nucleotides to enhance [3H]XAC binding was GTP = Gpp(NH)p greater than GDP greater than GDP beta S = cGMP, which paralleled their ability to inhibit forskolin-stimulated adenylate cyclase activity. Saturation isotherms performed in the absence and presence of GTP and Gpp(NH)p indicate that the guanine nucleotide decreased the equilibrium dissociation constant (KD) but had no effect on the maximal binding (Bmax) of [3H]XAC. In contrast, Gpp(NH)p decreased agonist binding as manifested by a decrease in the percentage of A1 adenosine receptors in the agonist high affinity state (from 81% to 27%) without changing the high (KH) and low (KL) affinity constants. Kinetic experiments conducted to assess the effect of guanine nucleotide on [3H]XAC binding parameters demonstrate that Gpp(NH)p enhanced the observed rate of association (Kobs) of the radioligand with the receptor by 2-fold but had no effect on the rate of dissociation (K-1) of the radioligand-receptor complex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reciprocal modulation of agonist and antagonist binding to A1 adenosine receptors by guanine nucleotides is mediated via a pertussis toxin-sensitive G protein. 313 8

The effect of human tumor necrosis factor (TNF) on early-passage HL-60 cells was studied. A transient phase of increased [3H]thymidine (TdR) incorporation was noted at 20-24 hr of exposure to TNF. This increase was disproportionate to the much slighter stimulation of the percentage of S-phase cells, which was measured by flow cytometry. Evidence for increased metabolic trapping of [3H]TdR following TNF treatment was apparent from whole cell uptake experiments. The salvage pathway enzyme TdR kinase was therefore measured and was found to be elevated comparably to [3H]TdR uptake. The mechanism of TNF regulation of TdR kinase was further investigated by a series of combination treatment experiments using other biologic factors and pharmacologic inhibitors of various intracellular steps. The response to TNF was not potentiated or reproduced by IL-1, IL-2, IL-3, IL-4, G-CSF, M-CSF, GM-CSF or alpha- or gamma-interferon. Blockers of early signal transduction steps, including H7, W7, sphingosine, and pertussis toxin, failed to inhibit TNF stimulation of [3H]TdR incorporation. mRNA synthesis inhibition with alpha-amanitin blocked this TNF effect, as did cAMP but not cGMP analogues. A sensitizing effect was noted with amiloride or cytochalasin B, characterized by greater relative increases of [3H]TdR incorporation and TdR kinase activity in response to TNF. In the presence of cytochalasin B, TNF treatment resulted in no change or slight decreases in the percentage of S-phase cells. Regulation of TdR kinase could thereby be dissociated from the usual cell cycle control. This study thus documents a unique example of stimulation of thymidine salvage pathway metabolism by a biologic factor, dissociable from overall cell cycle regulation.
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PMID:Stimulation by tumor necrosis factor of HL-60 thymidine salvage pathway metabolism dissociated from proliferation. 316 95


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