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)

The neuroblastoma line SK-N-SH consists of distinct and interconverting cell types, which include a neuroblast phenotype (SH-SY5Y), an epithelial phenotype (SH-EP), and an intermediate cell type (SH-IN). In SH-SY5Y cells, only muscarinic receptor activation produced stimulation of phosphoinositide turnover, whereas in SH-EP cells, where muscarinic receptors are not present, the peptides bradykinin, endothelin, and angiotensin II stimulated phosphoinositide hydrolysis with EC50 values of 16, 6, and 0.7 nM, respectively, and a rank order of maximal effects of bradykinin greater than endothelin greater than angiotensin II. Fetal calf serum at concentrations between 1 and 10% was also a potent stimulator of phosphoinositide hydrolysis in SH-EP cells but not in SH-SY5Y cells. In the intermediate cell clone, SH-IN, phosphoinositide hydrolysis was stimulated not only by muscarinic receptors, but also by endothelin, bradykinin, and serum, an indication that this cell type harbors all the kinds of receptors that are differentially expressed in the other two cell types. The effects of the three peptides--bradykinin, endothelin, and angiotensin II--on phosphoinositide hydrolysis in SH-EP cells were additive, a result suggesting that the three kinds of receptors may activate distinct transducer proteins and/or phospholipase C subtypes. Pretreatment of intact SH-EP cells with pertussis toxin under conditions sufficient to ADP-ribosylate 90-95% of the endogenous guanine nucleotide regulatory protein substrates did not impair the ability of any of the receptors to stimulate phosphoinositide hydrolysis in any of the cell types. In contrast, short-term exposure to the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (1 microM) abolished the stimulation of phosphoinositide hydrolysis mediated by peptide receptors in SH-EP cells and partially inhibited that by muscarinic receptors in SH-SY5Y cells. Prolonged incubation of SH-EP cells with phorbol ester resulted in a recovery of receptor responsiveness, the extent and rate of which were different for each receptor type. In contrast, there was no recovery of responsiveness for muscarinic receptors in SH-SY5Y cells. The pattern of phorbol ester-mediated effects depended on the cell rather than on the receptor type. In fact, muscarinic receptor responsiveness in SH-IN, the intermediate cell type, was desensitized by and recovered from treatment with phorbol esters in a manner more similar to peptide receptors in SH-EP than to muscarinic receptors in SH-SY5Y. These data suggest that the transduction mechanisms by which distinct receptor types are coupled to phosphoinositide hydrolysis in the three cell phenotypes differ in sensitivity to feedback regulation by protein kinase C.
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PMID:The epithelial phenotype of human neuroblastoma cells express bradykinin, endothelin, and angiotensin II receptors that stimulate phosphoinositide hydrolysis. 130 39

The expression of subunits of the guanine nucleotide regulatory protein that mediates hormonal stimulation of adenylyl cyclase (Gs) and of the guanine nucleotide regulatory protein that mediates hormonal inhibition of adenylyl cyclase (Gi) was studied during cell migration and differentiation in the rat small intestine crypt-villus axis. Proliferative crypt cells were separated from nonproliferative mature villus cells and the following data were obtained: 1) alpha s subunits were more abundant in crypt cells than in villus cells as evidenced by cholera toxin-catalyzed [32P]NAD ribosylation and Western blotting of this relative molecular weight (M(r)) 42,000 protein; 2) alpha i2- and alpha i3-subunits (M(r) 40,000 and M(r) 41,000, respectively) were preferentially expressed in villus cells as evidenced by pertussis toxin-catalyzed [32P]NAD ribosylation and Western blotting (alpha i1-subunit was not detectable in intestinal epithelium by using these techniques); 3) Western blotting showed a higher expression of the common beta- (M(r) 36,000) subunit of G proteins in villus cells than in crypt cells; and 4) Northern blot analysis using an alpha s-subunit oligonucleotide probe showed a 1.9-kb mRNA that was more abundant in crypt cells than in villus cells. In contrast, alpha i2- and alpha i3-mRNA species (2.3 and 3.5 kb, respectively), analyzed by using specific cDNA probes, were much more abundant in villus cells than in crypt cells. Finally, two beta-subunit mRNA species of 3.3 and 1.8 kb were detectable in intestinal epithelial cells and were more abundant in villus cells than in crypt cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gs and Gi protein subunits during cell differentiation in intestinal crypt-villus axis: regulation at the mRNA level. 137 46

A guanine nucleotide regulatory protein (G-protein) was purified to homogeneity from rat brain membrane though a series of chromatography runs, including DE-52 ion exchange, AcA-34 ultrogel, and octyl-Sepharose columns. The purified G-protein consisted of 3 subunits with molecular weights of 41000, 36000, and 8000, respectively. The alpha-subunit of the G-protein possessed high affinity GTP binding sites (k = 22.5 nmol/L) and GTPase activity (Km = 82.5 nmol/L, Vmax = 2.8 pmol/min/microgram protein), and it could be ADP-ribosylated by [adenylate-32P]-NAD in the presence of pertussis toxin. These results suggest that the purified protein was Gi-protein.
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PMID:The purification of a guanine nucleotide regulatory protein from rat brain membrane and the measurement of its GTPase. 145 Mar 95

This review outlines evidence that IL-1, IL-2, and TNFs modulate neutrophil functions. These cytokines affect some or all of the following functions of the neutrophil: adherence, cell migration, respiratory burst, lysosomal enzyme release, and cell surface receptor expression. TNFs, especially TNF alpha, remains one of the most highly studied cytokine with respect to regulation of neutrophil function. TNFs are a direct stimuli for the neutrophil respiratory burst and weak stimuli of lysosomal enzyme release. The cytokines enhance cell adhesion and inhibit neutrophil migration. The TNFs augment the oxidative burst and lysosomal enzyme release response to a wide range of soluble and particulate cell stimuli. These changes in the cell seem to be closely correlated with the increased fungicidal, bactericidal, tumoricidal, and protozoacidal activity of the TNF-primed neutrophils. In contrast to TNFs, IL-1 and IL-2 inhibit neutrophil adherence, and this provides evidence that the cytokine family represents a regulatory system. Another form of regulation of TNF alpha and IL-1 neutrophil-activating activity is by the release of inhibitors to these cytokines (58). We have evidence which shows that the soluble TNF alpha inhibitor (a cleaved product of the TNF alpha receptor) (59) binds and inhibits TNF from activating and priming neutrophils (60). Priming of neutrophils by TNFs involves surface receptor binding but is independent of protein kinase C system, pertussis toxin-sensitive guanine nucleotide regulatory protein, and direct burst of respiratory activity. The translocation of cell surface receptors and constituents of the NADPH oxidase from stored vesicles may be the major mechanism of TNF-induced cell priming.
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PMID:Activation of neutrophils by interleukins-1 and -2 and tumor necrosis factors. 150 43

Noradrenaline inhibits in rat islets the stimulation of insulin secretion induced by glucose and its potentiation by palmitate, but the signalling system responsible remains unknown. We have tested the hypothesis that noradrenaline-induced inhibition is mediated by an elevation of cyclic GMP (cGMP) levels. The analogue 8-Br-cGMP decreases dose-dependently the potentiation by palmitate of glucose-induced insulin secretion, whereas it only slightly affects the proper effect of glucose. Similarly, it abolishes palmitate acceleration of glucose-induced 45Ca2+ uptake without modifying the sugar effect. Finally, 8-Br-cGMP completely inhibits the stimulation of the lipid synthesis de novo induced by palmitate, but not that caused by glucose alone. On the other hand, noradrenaline increases dose-dependently islet cGMP content, with alpha 2-adrenergic specificity. As noradrenaline-induced elevation of cGMP is sensitive to pertussis toxin, it probably results from alpha 2-adrenoceptor activation of islet guanylate cyclase through a guanine nucleotide regulatory protein. It is concluded that the elevated cGMP levels mediate noradrenaline inhibition of lipid synthesis de novo, and hence of acceleration by palmitate of 45Ca2+ uptake and insulin secretion in the presence of glucose.
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PMID:Does cyclic guanosine monophosphate mediate noradrenaline-induced inhibition of islet insulin secretion stimulated by glucose and palmitate? 165 40

The role of guanine nucleotide-binding proteins in the induction of prostacyclin synthesis by stimulated endothelial cells is incompletely understood. We report that sodium fluoride (NaF), a potent activator of cellular guanine nucleotide-binding proteins, affected time- and concentration-dependent generation of prostacyclin (PGI2) by cultured human umbilical vein endothelial cells without evidence of cellular toxicity detected by 51Cr or lactate dehydrogenase release. PGI2 synthesis by NaF-stimulated endothelial cells was associated with increases in arachidonate release, phosphoinositide hydrolysis, generation of inositol phosphates, and accumulation of diacylglycerol. These responses to NaF, as well as alpha-thrombin-mediated responses, were not dependent upon the availability of extracellular free Ca2+ but were associated with the mobilization of stored intracellular Ca2+ detected by the luminescence of the photoprotein aequorin. Neither PGI2 synthesis nor Ca2+ responses following alpha-thrombin or NaF stimulation were inhibited by pretreatment of cells with the islet activating protein from Bordetella pertussis but were significantly attenuated by the G protein inhibitor GDP beta S in permeabilized cells. Our results are compatible with a model wherein NaF directly activates a phosphoinositidase-linked guanine nucleotide regulatory protein, Gp, in human umbilical vein endothelial cell monolayers. This activation results in phosphoinositide hydrolysis, Ca2+ mobilization, arachidonate release, and subsequent functional activation, assessed by PGI2 release. Biologically relevant agonists such as alpha-thrombin may exert their influence on arachidonate metabolism, in part, by promoting receptor-dependent activation of this G protein.
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PMID:Sodium fluoride induces phosphoinositide hydrolysis, Ca2+ mobilization, and prostacyclin synthesis in cultured human endothelium: further evidence for regulation by a pertussis toxin-insensitive guanine nucleotide-binding protein. 165 60

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

Propranolol inhibited cyclic AMP (cAMP) accumulation stimulated by 3-isobutyl-1-methylxanthine (IBMX) or forskolin in rat parotid acinar cells. The inhibition by propranolol was highly potent; 10(-7) M propranolol was sufficient for the maximum inhibition (approx. 50% at 5 min). The inhibitory effect was observed in both intact and saponin-permeabilized parotid cells, but the effect was more prominent in permeabilized cells than in intact cells. Other beta-blockers, like alprenolol and atenolol, were as effective as propranolol, but butoxamine (beta 2-selective) was slightly less effective. The inhibition by propranolol was similarly detected in the cells prepared from pertussis-toxin-pretreated rats, suggesting that inhibitory guanine nucleotide regulatory protein (Gi) is not involved in the inhibitory mechanism. Propranolol also inhibited the exocytosis of amylase stimulated by IBMX or forskolin. In the presence of propranolol and IBMX, the responsiveness of saponin-permeabilized cells to exogenous cAMP was markedly increased, indicating that propranolol neither promotes the degradation of cAMP nor prevents the inhibitory effect of IBMX on cAMP phosphodiesterase.
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PMID:Propranolol inhibits cyclic AMP accumulation and amylase secretion in parotid acinar cells stimulated by isobutylmethylxanthine and forskolin. 169 60

In this study, we report the effect of pertussis toxin pretreatment on dihydropyridine modulation of voltage-sensitive calcium channels in PC12 cells. The rise in intracellular calcium concentration caused by potassium depolarization is not affected significantly by pertussis toxin pretreatment. Nicardipine, a dihydropyridine derivative, added either before or after potassium-induced depolarization, reduces the resultant elevation in cytosolic calcium level both in control and in pertussis toxin-treated cells. The dihydropyridine agonist Bay K 8644, when added before potassium, is able to enhance the potassium-induced spike of cytosolic calcium levels, an effect significantly reduced by pertussis toxin pretreatment. Moreover, the addition of Bay K 8644 after potassium holds the intracellular calcium concentration at a cytosolic sustained level during the slow inactivating phase of depolarization. This effect of Bay K 8644 is inhibited by nicardipine. Pertussis toxin pretreatment slightly weakens the effect of Bay K 8644 when added after potassium-induced depolarization, whereas it significantly reduces the nicardipine inhibition of cytosolic calcium rise stimulated by potassium and Bay K 8644, but not by potassium alone. In conclusion, our findings suggest that a pertussis toxin-sensitive guanine nucleotide regulatory protein could be involved in the interaction between dihydropyridine derivatives and voltage-dependent calcium channels.
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PMID:Dihydropyridine modulation of voltage-activated calcium channels in PC12 cells: effect of pertussis toxin pretreatment. 170 21

A pertussis toxin-sensitive guanine nucleotide regulatory protein (G-protein) is involved in the signal transduction of certain endothelium-dependent responses in mammalian arteries. To determine whether a similar mechanism mediates endothelium-dependent responses in mammalian veins, rings of canine femoral arteries and veins with and without endothelium were suspended for the measurement of isometric force in organ chambers. In femoral arteries, incubation of the rings with pertussis toxin (from Bordetella pertussis, 100 ng/ml for 2 hr) in the presence of indomethacin and propranolol did not reduce significantly endothelium-dependent relaxations to acetylcholine and adenosine diphosphate, thrombin or the calcium ionophore A23187. However, endothelium-dependent relaxations evoked by the alpha-2 adrenergic agonist UK 14,304 were blocked by the pertussis toxin. In venous rings, endothelium-dependent relaxations to acetylcholine were reduced by the toxin, whereas the endothelium-dependent relaxations evoked by adenosine diphosphate, thrombin and A23187 were not affected. UK 14,304 contracted the veins; these contractions were augmented by removal of the endothelium. Pertussis toxin inhibited contractions to UK 14,304 in venous rings without but not with endothelium. Relaxations of arterial and venous smooth muscle to nitric oxide were unaffected by the toxin. Contractions to phenylephrine were not altered by either removal of the endothelium or the toxin in the arteries or veins. These results suggest that the release of endothelium-derived relaxing factor in response to stimulation of purine and thrombin receptors probably does not involve a pertussis toxin-sensitive G-protein in canine femoral arteries or veins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pertussis toxin reduces endothelium-dependent and independent responses to alpha-2- adrenergic stimulation in systemic canine arteries and veins. 185 Apr 67


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