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

The direct action of somatostatin on smooth muscle was examined in muscle cells isolated from the stomach and intestine of human and guinea pig. Somatostatin inhibited relaxation in gastric but not intestinal muscle cells of the two species, and its mechanism of action was explored in more detail in gastric muscle cells of the guinea pig. Somatostatin inhibited relaxation induced by vasoactive intestinal peptide (VIP, 83 +/- 7%, P less than 0.001) and isoproterenol (85 +/- 5%, P less than 0.001), as well as the concomitant increase in adenosine 3',5'-cyclic monophosphate (cAMP) production [81 +/- 25% inhibition with VIP (P less than 0.02) and 68 +/- 12% inhibition with isoproterenol (P less than 0.01)]. Inhibition of relaxation and cAMP production was abolished by pretreatment of the cells with pertussis toxin. Relaxation induced by the permeant derivative of cAMP, N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate, by sodium nitroprusside, which acts by increasing levels of guanosine 3',5'-cyclic monophosphate, or by ATP, which acts by opening of K+ channels, was not affected by somatostatin. The fact that inhibition by somatostatin and its reversal by pertussis toxin was confined to agonists that stimulate an increase in the levels of cAMP implied that somatostatin acts by inhibiting the generation and not the action of cAMP. It is concluded that somatostatin receptors on gastric muscle cells mediate inhibition via a GTP-binding, pertussis-sensitive regulatory protein, Gi, coupled to adenylate cyclase.
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PMID:Inhibition of muscle cell relaxation by somatostatin: tissue-specific, cAMP-dependent, pertussis toxin-sensitive. 167 35

Cholera and pertussis toxin-mediated ADP-ribosylation has been used extensively to study regulation of guanine nucleotide binding proteins (G proteins) in the nervous system, but much less is known about possible endogenous ADP-ribosylation of G proteins in brain. The present study demonstrates endogenous ADP-ribosylation, in the absence of cholera and pertussis toxins, of four predominate proteins in homogenates of rat cerebral cortex. These proteins showed apparent molecular masses of 20, 42, 45, and 50 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The 42- and 45-kDa proteins comigrated precisely with the major cholera toxin-labeled bands. Furthermore, the endogenous ADP-ribosylated and cholera toxin-ADP-ribosylated bands yielded identical 32P-labeled peptide fragments by one-dimensional peptide mapping, indicating that they are probably the same proteins, presumably the alpha-subunits of Gs. In contrast, peptide maps of the 50-kDa protein, which migrated close to a 48-kDa cholera toxin-labeled band, demonstrated that this protein is distinct from the toxin-labeled band and from Gs alpha. Levels of endogenous ADP-ribosylation activity showed regional heterogeneity in brain, with a nearly threefold variation observed among the brain regions examined. Chronic administration (7 days) of corticosterone significantly increased overall levels of endogenous ADP-ribosylation, indicating that components of this system may be under hormonal control in vivo. Attempts to identify neurotransmitters or second messenger systems that regulate endogenous ADP-ribosylation activity in brain have so far been unsuccessful with one exception.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endogenous ADP-ribosylation in brain: initial characterization of substrate proteins. 168 21

Atrial natriuretic peptide, acting through its second messenger guanosine 3',5'-cyclic monophosphate (cGMP), suppresses Na+ absorption across the renal inner-medullary collecting duct and increases urinary Na+ excretion. Patch clamp studies show that cGMP reduces Na+ absorption by inhibiting an amiloride-sensitive cation channel in the apical membrane. We have now examined, using the patch clamp technique, the molecular mechanisms of cGMP inhibition. Cyclic GMP directly and specifically reduced the probability of a single channel being open (open probability, Po) by 39% (inhibition constant, Ki = 7.6 x 10(-7) M) by a phosphorylation-independent mechanism. Cyclic GMP also inhibited the channel by activating cGMP-dependent protein kinase (cGMP-kinase). Exogenous cGMP-kinase completely inhibited the channel by a phosphorylation-dependent mechanism. Activation of a pertussis toxin-sensitive G protein by GTP-gamma-S blocked cGMP-kinase inhibition of the channel. By contrast, cGMP-kinase inhibition of Po was completely reversed by GTP-gamma-S. Taken together with the results of a previous study showing that a G protein activates the cation channel, these data indicate that cGMP-kinase and a G protein sequentially regulate the cation channel. Our results show that atrial natriuretic peptide, acting through cGMP, inhibits Na+ absorption across the inner-medullary collecting duct by a dual mechanism, and that cGMP-kinase inhibits the channel by a pathway involving a G protein.
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PMID:Dual ion-channel regulation by cyclic GMP and cyclic GMP-dependent protein kinase. 169 Mar 55

Elevation of cellular cyclic AMP by agents such as isoproterenol plus 3-isobutyl-1-methylxanthine produced rapid and reversible dendritic formation of bovine pulmonary artery endothelial cells in the monolayer. The effect did not occur with exposure of the cells to a variety of other vasoactive agents, calcium ionophore, phorbol ester, or cyclic GMP. The cyclic AMP-induced configurational change was completely inhibited by 2.5 mM N-phenylanthranilic acid or 145 mM sodium gluconate (Cl- channel inhibitors) and was partially inhibited by 2.5 mM 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS), but it was not affected by deprivation of Ca2+ or Na+ ion, 1 mM bumetanide (Cl- cotransport inhibitor), 1 mM amiloride (Na+/H+ exchange inhibitor), 0.1 mM verapamil (Ca2+ channel inhibitor), or 5 mM BaCl2 (K+ channel inhibitor), by change in cellular pH, or by pertussis toxin. Trifluoperazine (calmodulin inhibitor, 50 microM), 1 mM EGTA plus 100 microM 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8, intracellular Ca2+ antagonist), and 5 microM cytochalasin B also produced cellular retraction, but these changes were not blocked by chloride channel inhibition. In the presence of 0.1 mM ouabain plus 0.1 mM bumetanide, 36Cl- uptake was decreased by isoproterenol plus isobutylmethylxanthine while its efflux was enhanced. N-Phenylanthranilic acid inhibited the stimulated efflux. We conclude that cyclic AMP induces a configurational change of endothelial cells that is related to Cl- efflux from the cells; the cellular effects may play a role in vascular function.
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PMID:Chloride efflux in cyclic AMP-induced configurational change of bovine pulmonary artery endothelial cells. 169 Jun 13

The renal epithelial cell line LLC-PK1 has topographically distinct regulatory roles for the alpha subunits of pertussis toxin-sensitive guanine nucleotide regulatory proteins (alpha i subunit); these include the inhibition of adenylyl cyclase at the basolateral membrane and the stimulation of Na+ channel activity at the apical membrane. We now report that LLC-PK1 cells contain two members of the alpha i protein family, alpha i-2 and alpha i-3, which have distinct cellular locations consistent with their diverse functional roles. By using specific alpha i antibodies and immunofluorescence, the alpha i-2 subunit was found to be localized to the basolateral membrane, whereas the alpha i-3 subunit was concentrated in the Golgi and was also detectable at low levels on apical membranes in some cells. Induction of a chimeric mouse metallothionein 1-rat or canine alpha i-2 gene stably transfected into the LLC-PK1 cells produced an increase in the content of the alpha i-2 subunit, which was targeted only to the basolateral membrane. These findings suggest that alpha i subunit specificity for effectors may be achieved in polarized renal epithelial cells by their geographic segregation to different cellular membranes. The LLC-PK1 cell stably transfected with the metallothionein-alpha i-2 fusion gene will provide a model for the study of guanine nucleotide regulatory protein function in epithelia.
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PMID:Membrane localization of the pertussis toxin-sensitive G-protein subunits alpha i-2 and alpha i-3 and expression of a metallothionein-alpha i-2 fusion gene in LLC-PK1 cells. 169 74

A rapid two-step purification to homogeneity of the calmodulin-activated adenylyl cyclase from urea extracts of Bordetella pertussis organisms (strain 114) is described. Catalytic and invasive activities are purified 30- and 177-fold, respectively, and virtually no degraded forms are found. Specific activities are 0.4 mmol/min/mg and 0.5 mumol/mg of enzyme protein/mg of cell protein/min for catalytic and invasive activities, respectively. The 15 amino-terminal amino acids agree with those deduced from the DNA sequence, as does the molecular mass of 175 kDa (guanidine) or 177 kDa (urea) obtained by equilibrium sedimentation. The larger apparent molecular mass seen in sodium dodecyl sulfate-polyacrylamide gel electrophoresis can be ascribed to anomalous migration. Half-maximal cyclase activation occurs at 3-4 X 10(-10) M calmodulin in the presence of Ca2+ and at 2 X 10(-8) M calmodulin in its absence. Ca2+ activation is maximal at 60-100 microM free CaCl2 (at low calmodulin concentrations), and free Ca2+ concentrations above approximately 125 microM are inhibitory at any calmodulin concentration. Extracellular Ca2+ is essential for intoxication. In Chinese hamster ovary cells, exogenous calmodulin does not inhibit penetration of the cyclase.
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PMID:Invasive adenylyl cyclase of Bordetella pertussis. Physical, catalytic, and toxic properties. 169 22

Acetylcholine (ACh) depolarizes the membrane of mammalian intestinal myocytes by activating a nonselective cation channel (G. D. Benham, T. B. Bolton, and R. J. Lang. Nature Lond. 316: 345-347, 1985; R. Inoue, K. Kitamura, and H. Kuriyama. Pfluegers Arch. 410: 69-74, 1987). Here, we present evidence that occupation of the muscarinic receptor by ACh couples to channel activation via a G protein; the coupling can be blocked by pertussis toxin or by intracellular guanosine 5'-O-(2-thio-diphosphate) (GDP beta S), whereas intracellular guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) activates the channel in the absence of ACh. The currents, activated by either ACh or GTP gamma S, are nonadditive, conduct sodium ions, and are similar in their voltage dependence and facilitation by submicromolar calcium ions in the cytosol.
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PMID:Acetylcholine activates nonselective cation channels in guinea pig ileum through a G protein. 169 99

When applied extracellularly in the micromolar range, ATP and related compounds induced a positive inotropy in the rat papillary muscle. This was also true in the rat auricle after pertussis toxin treatment. Then, in both tissues, ATP further increased the contraction after a maximal beta-adrenergic stimulation. The increase in contractile force could be related to the increase in the calcium current. The L-type calcium current was measured by whole-cell patch-clamp recording in single cells isolated from the rat ventricle after the sodium and potassium currents were inhibited by tetrodotoxin and cesium, respectively. When added alone, 10 microM ATP increased the calcium current by 60%. Adenosine 5'-O-(3-thiotriphosphate) was also able to increase calcium current. Adenosine was much less effective, and GTP, UTP, CTP, and ITP were without effect. A similar increase in calcium current was observed when ATP was added in addition to a maximal stimulation by a beta-adrenergic agonist or after internal perfusion with cyclic AMP. However, this increase was preceded by a transient decrease whose origin could not be attributed to a P1-purinergic agonistic effect of ATP. The transient decrease was not elicited by adenosine or in a magnesium-free HEPES solution and was not suppressed after pertussis toxin treatment. This effect appeared related to the variations in the holding current also observed upon ATP application. Together with vasodilation, ATP and adenine compounds induced positive inotropy. The latter effect could be attributed in part to the increase in calcium current and was independent of cyclic AMP. Both effects are complementary with the beta-adrenergic stimulation and can help healthy cells to compensate the failing zone from which ATP could be released.
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PMID:The mechanism of positive inotropy induced by adenosine triphosphate in rat heart. 169 71

The involvement of G-proteins in the insulin signal transduction system has been studied in detail using the murine BC3H-1 myocyte system. Pertussis toxin (PT) treatment, previously shown to attenuate some of the metabolic effects of insulin in this cell line (Luttrell, L.M., Hewlett, E.L., Romero, G., and Rogol, A.D. (1988) J. Biol. Chem. 263, 6134-6141), abolished insulin-induced generation of diacylglycerol and inositolglycan mediators with no effects on either the autophosphorylation of the insulin receptor or the phosphorylation of the major endogenous substrates for insulin-stimulated tyrosine kinase activity (pp185 and pp42-45). In vitro ADP-ribosylation and immunoblotting studies suggest that the major PT substrate is a 40-kDa protein of the G alpha family. This protein band did not exhibit detectable tyrosine phosphorylation upon stimulation of either intact cells or cell membranes with insulin. In the presence of low concentrations of GTP, insulin treatment of isolated myocyte plasma membranes resulted in a small (30-40%) but significant stimulation of GTP hydrolysis. This effect was best observed in the presence of small concentrations of sodium dodecyl sulfate. The rate of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) binding to BC3H-1 membranes was also significantly increased in the presence of insulin. The effects of insulin on GTP hydrolysis and GTP gamma S binding were found to be dependent on the concentration of insulin. These effects were not detected in plasma membranes prepared from PT-pretreated BC3H-1 myocytes. In contrast, pretreatment with the B (inactive) subunit of PT did not alter the response of myocyte membranes to insulin. High affinity binding of [125I]iodoinsulin to myocyte plasma membranes was reduced by 60-70% in the presence of guanine nucleotides. Similar effects on insulin binding were produced by PT pretreatment of the cells. In contrast, adenine nucleotides had no effect on insulin binding. Scatchard analysis of the binding data showed that the observed effects of guanine nucleotides and PT on insulin binding resulted either from a reduction in the number of high affinity insulin binding sites or from a significant reduction of the affinity of insulin for its receptor. Low affinity binding sites did not appear to be affected by either guanine nucleotides nor PT pretreatment. These results provide substantial evidence suggestive of a noncovalent interaction between the insulin receptor and a regulatory G-protein system during the process of insulin signaling.
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PMID:A pertussis toxin-sensitive G-protein mediates some aspects of insulin action in BC3H-1 murine myocytes. 169 70

1. Membrane currents were recorded by a patch-clamp pipette technique in cultured cells from rat portal vein using the whole-cell mode. 2. Noradrenaline (NA, 10(-5) M) and phorbol-12,13-dibutyrate (PDBu, 10(-7) M) produced an increase in voltage-dependent inward current carried by barium (5 mM), but their effects were not additive. Calcium-activated chloride current was evoked by NA but not by PDBu. 3. The NA-induced increase in peak voltage-dependent inward current was inhibited by intracellular application of GDP-beta-S (10(-3) M) while the effect of PDBu was unchanged. GDP-beta-S blocked the NA-induced chloride current but had no effect on the caffeine-induced chloride current. 4. Inclusion of GTP-gamma-S (10(-5)-10(-4) M) in the pipette solution increased the voltage-dependent inward current and inhibited the NA- or PDBu-induced increase in peak current. GTP-gamma-S potentiated the effect of NA on calcium-activated chloride current. At higher concentrations (10(-3) M), GTP-gamma-S activated the chloride current and prevented the effects of NA or caffeine on this current. 5. The combination of 10(-5) M-aluminium chloride and 10(-2) M-sodium fluoride had an effect similar to that of high concentrations of GTP-gamma-S on both inward current and calcium-activated chloride current. In contrast, arachidonic acid (10(-3) M) had no effect on calcium and chloride conductances activated by NA. 6. Cells responded normally to NA after pre-treatment for 4-30 h with 10 micrograms ml-1 pertussis toxin (PTx). 7. It is concluded that the stimulation of calcium and chloride conductances by NA is mediated through activation of a PTx-insensitive GTP-binding protein. This effect may involve activation of phospholipase C enzyme and production of both D-myo-inositol 1,4,5-trisphosphate which depletes calcium stores and diacylglycerol which activates protein kinase C.
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PMID:GTP-binding proteins mediate noradrenaline effects on calcium and chloride currents in rat portal vein myocytes. 170 Jan 11


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