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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of an adenosine A1-receptor agonist and antagonist were determined in pertussis toxin (IAP)-treated and non-treated rats. (-)-N6-(2-phenylisopropyl) adenosine, an adenosine A1-agonist, reduced the urine volume and sodium excretion without decreasing the glomerular filtration rate at 0.1 mg/kg (p.o.) in both IAP-treated and non-treated rats. Diuretic effects of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine) and 8-cyclopentyl-1,3-dipropylxanthine, adenosine A1-receptor antagonists, were not affected by pretreatment with IAP. These results suggest that endogenous adenosine may induce antidiuretic effects by accelerating the reabsorption of water and sodium at tubular sites via an IAP-insensitive mechanism, and that the diuretic effects of the adenosine A1-receptor antagonist may result from inhibiting this action of endogenous adenosine.
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PMID:Effects of adenosine A1-agonist and -antagonist on urinary volume and Na excretion in IAP-treated and non-treated rats. 828 37

KW-3902 [8-(noradamantan-3-yl)-1,3-dipropylxanthine] is a novel potent and selective adenosine A1-receptor antagonist. In anesthetized rats, KW-3902 (0.1 and 1 mg/kg p.o.) antagonized the 5'-N-ethylcarboxamidoadenosine (NECA) induced bradycardic response, which is thought to be mediated via adenosine A1-receptors. However, the hypotensive response to NECA, which is predominantly due to adenosine A2-receptor activation, was not affected by KW-3902. Diuretic and renal protective effects of KW-3902 were investigated in normal and pertussis toxin (IAP; 10 micrograms/kg i.v.)-treated rats. KW-3902 (0.001-1 mg/kg p.o.) caused significant increases of urine volume and sodium excretion with little change of potassium excretion in saline-loaded normal rats. In anesthetized normal rats, KW-3902 (0.01 and 0.1 mg/kg i.v.) caused significant diuresis and natriuresis with no change in renal plasma flow and glomerular filtration rate. These findings suggest that KW-3902 caused the diuretic effect not by the change in the renal hemodynamics, but by the inhibition of water and sodium reabsorption in tubular sites. KW-3902 (0.01-1 mg/kg p.o.) significantly attenuated increases of serum creatinine and urea nitrogen and renal tubular damage in glycerol-induced acute renal failure rats. Neither diuretic nor renal protective effects of KW-3902 were affected by pretreatment of rats with IAP, which totally abolished the bradycardic response to NECA. These results are compatible with the hypothesis that diuretic and renal protective effects by adenosine A1-receptor blockade are mediated via IAP-insensitive mechanism.
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PMID:Diuretic and renal protective effects of 8-(noradamantan-3-yl)-1,3-dipropylxanthine (KW-3902), a novel adenosine A1-receptor antagonist, via pertussis toxin insensitive mechanism. 833 58

The rat basophilic leukemia (RBL) mast cell line possesses cell surface receptors for adenosine whose ligation markedly potentiates antigen-driven Ca2+ influx and secretion. Here we show that engagement of these receptors and of separate P2 purinergic receptors rapidly activates an outwardly rectifying K+ conductance [GK(OR)] in RBL cells. Activation of GK(OR) by the ligands 5'-(N-ethylcarboxamido)adenosine (NECA), ADP, and ATP was prevented by cytoplasmic guanosine 5'-[beta-thio]diphosphate as well as by pretreatment of the cells with pertussis toxin, implicating mediation by a G protein. Multiple cycles of induction and decay of GK(OR) were produced upon application and removal of ligand. Induction of GK(OR) by either ligand was much faster than the induction caused by guanosine 5'-[gamma-thio]triphosphate (t1/2 < 10 sec vs. 210 sec.). In control cells the maximal whole-cell conductance elicited by ADP (2.25 +/- 0.30 nS) or ATP (2.50 +/- 0.33 nS) was about twice as large as that induced by NECA (1.03 +/- 0.11 nS), and similar to that previously reported for the guanosine 5'-[gamma-thio]triphosphate-elicited GK(OR) in RBL cells (2.58 +/- 1.59 nS). Treatment of RBL cells with dexamethasone upregulated Ca2+ responses to NECA, and it also nearly doubled the maximal conductance elicited by NECA without appreciable effect on responses to ADP or ATP. The failure of water-soluble second messengers to activate GK(OR) and the inability of 11 mM EGTA (< 10 nM Ca2+) to prevent activation by ADP suggest that the relevant pathway is membrane-delimited. Two ion-channel blockers inhibited antigen-stimulated secretion with IC50 values similar to those at which they blocked GK(OR), suggesting that activity of the outwardly rectifying K+ channel may be important for stimulus-response coupling in these cells. Potentiation of the secretory response by NECA may reflect, in part, the activation of GK(OR), which serves to repolarize the membrane more effectively than does the constitutive mechanism, thereby enhancing antigen-driven Ca2+ influx. This channel and its functionally associated receptors may allow neighboring cells of the host to modulate the response of mast cells to exogenous antigen.
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PMID:Activation of mast cell K+ channels through multiple G protein-linked receptors. 835 92

We isolated the opercular epithelium of sea-water killifish (Fundulus heteroclitus) to study the mediation of catecholamine inhibition of Cl- secretion. The receptors are alpha 2-adrenergic, as they have a high affinity for the alpha 2-adrenergic agonist clonidine over phenylephrine and clonidine action is blocked by yohimbine. Pertussis toxin and indomethacin did not block the clonidine effect; hence inhibitory guanine nucleotide-binding proteins (Gi proteins) and prostaglandins (respectively) are not involved. Intracellular pH (pHi) of single chloride cells was measured microspectrofluorometrically and resting pHi was 7.22 +/- 0.03. However, pHi was unaffected by clonidine; hence pHi and Na+/H+ exchange are not involved. The lipoxygenase inhibitors nordihydroguaiaretic acid and baicalein and the lipoxygenase products (12S)- and (12R)-12-hydroxyeicosatetraenoic acid stimulated Cl- secretion. Protein kinase C is an unlikely site of action because the diacylglycerol kinase inhibitor R59022 had no effect alone and did not block the clonidine effect. Ionomycin (1 microM) in normal but not low-Ca2+ solutions mimicked the action of clonidine and both inhibitions were reversible by isoproterenol. Thapsigargin, a releaser of intracellular Ca2+, inhibited Cl- secretion and this effect was reduced in low-Ca2+ solutions. Low-Ca2+ solutions also blunted but did not block entirely the clonidine response, indicating that the primary Ca2+ release was from intracellular stores. Whereas alpha 1-adrenergic receptors commonly act via the Ca2+/inositol trisphosphate pathway, to our knowledge this is the first report of a Ca(2+)-mediated alpha 2-adrenergic response in a nonmammalian vertebrate.
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PMID:Alpha 2-adrenergic inhibition of Cl- transport by opercular epithelium is mediated by intracellular Ca2+. 839 Jun 69

A 34-amino acid peptide corresponding to residues 532-565 of Bacillus anthracis adenylate cyclase (P532-565), a calmodulin (CaM)-activated enzyme, was synthesized by solid phase method. Although not homologous to any known CaM binding sequence, P532-565 exhibits molecular features characteristic of this class of peptides: a higher proportion of basic and hydrophobic residues, segregated onto the two faces of the alpha-helical structure. Fluorescence measurements and gel retardation analysis showed that P532-565 binds CaM in a Ca(2+)-dependent manner, with a binding energy that represents 80% of the binding energy of the adenylate cyclase-CaM complex. Circular dichroism analysis showed that P532-565 exists in solution as a mixture of random-coil and alpha-helical structures and that trifluoroethanol increases the relative proportion of alpha-helical population. Analysis of proton NMR spectrum in H2O allowed identification of the different amino acid spin systems and complete spectral assignment. The pattern of nuclear Overhauser effect connectivities, intense NN(i,i + 1) and medium range alpha N(i,i + 3) and alpha beta (i,i + 3) indicate the presence of an alpha-helix in the carboxylterminal end (between residues 551 and 563) in fast exchange with extended structures. These data, together with CaM-binding properties of Bordetella pertussis adenylate cyclase, show that despite rather divergent primary structures, the two bacterial enzymes possess similar structural organization of their binding sites for activator protein.
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PMID:Characterization of a synthetic calmodulin-binding peptide derived from Bacillus anthracis adenylate cyclase. 842 Sep 46

Pertussis toxin is a complex protein composed of five different subunits, named S1 through S5 and arranged in an A-B structure. The B oligomer, composed of S2 through S5, is the receptor-binding moiety, and the A promoter, composed of S1, is the enzymatically active moiety. S1 catalyzes the ADP-ribosylation of a cysteine in the alpha subunit of heterotrimeric G proteins. In the absence of G proteins it also catalyzes the cleavage of NAD+ into ADP-ribose and nicotinamide. Molecular dissection has indicated that the C-terminal domain of S1 is involved in G-protein binding, while the N-terminal domain, homologous to other ADP-ribosylating toxins, contains the NAD(+)-binding site and the residues involved in catalysis. By site-directed mutagenesis and kinetic analyses Glu-129 and His-35 were identified as the catalytic residues. Glutamates analogous to Glu-129 are found in all studied ADP-ribosylating toxins, while His-35 is less well conserved. This suggests that Glu-129 acts on the common substrate NAD+, whereas His-35 plays its role on the acceptor substrates. We propose a mechanism in which Glu-129 exerts its action on the 2'-OH group of the NAD+ ribose, thereby facilitating the formation of an oxocarbonium-like intermediate and the weakening of the N-glycosidic bond. His-35 could increase the nucleophilicity of the cysteine in the G protein or the water molecule to attack the weakened N-glycosidic bond of NAD+ and yield the products of the reaction.
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PMID:A proposed mechanism of ADP-ribosylation catalyzed by the pertussis toxin S1 subunit. 852 86

Members of the C-C family of chemotactic cytokines promote chemotaxis and adhesion of leukocytes. In this study, we have identified a murine T cell hybrid that expresses receptors to the chemotactic cytokine monocyte chemotactic protein-1 (MCP-1). This cell line was used to examine MCP-1 receptor-mediated signal transduction events in a homologous system in the absence of interference with other receptors. Our results show that in the 3B4 M1.9 T cell hybrid, MCP-1 receptors mediate intracellular calcium mobilization and extracellular calcium import without detectable increases in total water-soluble inositol phosphates. In addition, MCP-1 regulates the tyrosine phosphorylation of specific substrates at 42 and 44 kDa and induces mobility shift of p42/44 mitogen-activated protein kinases. MCP-1-mediated calcium responses, tyrosine phosphorylation, and the electrophoretic mobility shift of p42/44 mitogen-activated protein kinases can be inhibited by pretreatment of cells with pertussis toxin, indicating a role for Gi-like G proteins in coupling the MCP-1R to signal transduction.
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PMID:Early signal transduction by the receptor to the chemokine monocyte chemotactic protein-1 in a murine T cell hybrid. 856 34

Property of receptor for vasoactive intestinal contractor (VIC), a peptide related to the endothelin family, expressed in Xenopus oocytes by injecting mRNA obtained from the intestine of rat, were studied using the voltage-clamp method. Inward-current responses to VIC (1 nM-100 nM) were evoked in a concentration-dependent manner in mRNA-injected oocytes. Non-injected and water-injected oocytes failed to respond to VIC. The reversal potential for the VIC response was around -20 mV and the depolarizing shift was approximately 18 mV, when the external concentration of Cl-was halved, in agreement with the Nernst equation. The response to VIC was suppressed either by the external application to BAPTA/AM (10 microM) or by pertussis toxin 0.5 microgram/ml). These results indicate that the receptor for VIC, functionally expressed in Xenopus oocytes injected with rat intestinal mRNA, is coupled to pertussis toxin-sensitive G-protein and its activation leads to mobilization of intracellular Ca2+.
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PMID:Property of receptor for vasoactive intestinal contractor (VIC) expressed in Xenopus oocytes injected with mRNA from rat intestine. 863 97

Signal transduction of fibroblast growth factor (FGF) receptors is known to involve tyrosine phosphorylation of several substrates, including Grb2, phospholipase C-gamma, and phosphatidylinositol 3-kinase, whereas the role of G-proteins in FGF receptor signaling is controversial. In the present study we investigated the role of G-proteins in FGF receptor signaling in rat pancreatic acini. Immunological analysis revealed the presence of FGF receptor and phospholipase C-gamma1 in rat pancreatic acini. Both basic fibroblast growth factor (FGF-2) and guanosine 5'-(gamma-O-thio)triphosphate (GTPgammaS) caused an increase in inositol 1,4,5-trisphosphate (1,4,5-IP3) production and amylase release. Combined stimulation of the acini with GTPgammaS and FGF-2 led to a decrease of these responses as compared to the effect of the single substances. When pancreatic acini were preincubated with FGF-2 (1 nM) or vehicle (water) ADP-ribosylation of the alpha-subunit of Gi-type G-proteins by pertussis toxin was reduced in membranes prepared from FGF-2 pretreated acini as compared to control acini, suggesting functional interaction of FGF receptors with Gi-proteins. Pretreatment of acini with pertussis toxin which inhibits Gi-type G-proteins abolished the inhibitory effect of GTPgammaS on FGF-induced 1,4,5-IP3 production and amylase release, whereas the stimulatory effects of FGF-2 and GTPgammaS on these parameters remained unchanged. In conclusion, these results show communication of FGF receptors and Gi-type G-proteins and that Gi-type G-proteins exert an inhibitory influence on FGF-induced activation of phosphoinositide-specific phospholipase C in pancreatic acinar cells.
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PMID:Pertussis toxin-sensitive G-proteins inhibit fibroblast growth factor-induced signaling in pancreatic acini. 869 40

Mice exposed to cold water swimming (4 degrees C) for 3 min produced a marked antinociception. Experiments were designed to determine whether pretreatment with pertussis toxin given intrathecally (i.t.) or intracerebroventricularly (i.c.v.) attenuates cold water swimming-induced antinociception in male ICR mice. Antinociception was measured by the tail-flick test 7 min after cold water swimming. I.t. pretreatment with pertussis toxin at a dose of 0.5 microgram for 24-96 h caused a time-dependent attenuation of cold water swimming-induced antinociception. Moreover, i.t. pretreatment with pertussis toxin at doses from 0.125 to 0.5 microgram for 96 h attenuated cold water swimming-induced antinociception in a dose-dependent manner. However, i.c.v. pretreatment with pertussis toxin at doses from 0.125 to 0.5 microgram for 24-96 h did not affect the cold water swimming-induced antinociception. The present results suggest that pertussis toxin-sensitive Gi/G(o) proteins in spinal cord, but not at the supraspinal sites, are involved in cold water swimming-induced antinociception.
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PMID:Pretreatment with pertussis toxin spinally, but not supraspinally, blocks the cold water swimming-induced antinociception in the mouse. 886 91


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