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)

Pertussis toxin, islet-activating protein (IAP), and cholera toxin ADP-ribosylated 40 kDa and 45 kDa proteins in membrane preparations from Caenorhabditis elegans. Proteins with the same molecular weights were recognized in the same membranes by an antibody that had been raised against a peptide common to alpha-subunits of mammalian alpha beta gamma-heterotrimeric G proteins. The antibody produced immunoprecipitation with the 40 kDa protein 32P-labeled by IAP. A 35 kDa protein immunochemically indistinguishable from the beta-component of mammalian G proteins was also found in C. elegans membranes. The membranes displayed adenylate cyclase activity which was highly sensitive to forskolin and GTP analogues, whose action was antagonized by GDP beta S. Receptor-coupled regulation of adenylate cyclase thus appears to be mediated by mammalian-type G proteins in C. elegans as well.
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PMID:Probable occurrence of toxin-susceptible G proteins in the nematode Caenorhabditis elegans. 154 91

The possibility that a TSH post-receptor-binding defect is responsible for the pathogenesis of benign thyroid tumours was studied. Thus, we attempted to determine in hyperfunctioning (hot) nodules and non-functioning (cold) nodules whether the functional activity or the amount of G proteins were modified in comparison with surrounding normal tissues. The adenylyl cyclase response to agonists that bypass the TSH-receptor complex (forskolin, guanosine 5'- (beta.gamma-imido)triphosphate (Gpp(NH)p) or [AIF4]-) was studied on membranes from tumorous and adjacent normal thyroid tissues. We also examined the ability of G proteins to be ADP-ribosylated by cholera toxin (CT) or pertussis toxin (PT), and quantified G proteins by Western blot analysis with specific antisera directed against Gs alpha and Gi alpha subunits. Basal adenylyl cyclase activity was unchanged in hot tumours compared with normal tissue whereas the stimulation of adenylyl cyclase by Gpp(NH)p or [A1F4]- (which act directly on Gs) as well as by forskolin (which acts on the catalyst) was significantly (P less than 0.05) decreased in five of seven nodules studied. Two types of response were found in cold nodules, depending upon whether they were microfollicular or macrofollicular tumours. Basal as well as stimulated adenylyl cyclase activity was increased (0.02 less than P less than 0.05) in microfollicular tumours. In contrast, in macrofollicular tumours basal adenylyl cyclase was unchanged whereas stimulated adenylyl cyclase activity was decreased (0.02 less than P less than 0.05). The ability of Gs or Gi to be ADP-ribosylated by CT or PT respectively was maintained in tumorous tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modification of the amounts of G proteins and of the activity of adenylyl cyclase in human benign thyroid tumours. 156 34

We have used monolayers of control 3T3 cells and 3T3 cells expressing transfected human neural cell adhesion molecule (NCAM) or chick N-cadherin as a culture substrate for PC12 cells. NCAM and N-cadherin in the monolayer directly promote neurite outgrowth from PC12 cells via a G-protein-dependent activation of neuronal calcium channels. In the present study we show that ganglioside GM1 does not directly activate this pathway in PC12 cells. However, the presence of GM1 (12.5-100 micrograms/ml) in the co-culture was associated with a potentiation of NCAM and N-cadherin-dependent neurite outgrowth. Treatment of PC12 cells with GM1 (100 micrograms/ml) for 90 min led to trypsin-stable increases in both beta-cholera toxin binding to PC12 cells and an enhanced neurite outgrowth response to N-cadherin. The ganglioside response could be fully inhibited by treatment with pertussis toxin. These data are consistent with exogenous gangliosides enhancing neuritic growth by promoting cell adhesion molecule-induced calcium influx into neurons.
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PMID:Ganglioside modulation of neural cell adhesion molecule and N-cadherin-dependent neurite outgrowth. 157 68

Guanine nucleotide binding (G) proteins play a pivotal role in postreceptor information transduction. An important characteristic of G proteins is their increased guanine nucleotide binding following agonist stimulation, which in turn leads to their activation. We have developed a method that enables the measurement of early events in signal transduction beyond receptors, through activated receptor-coupled guanine nucleotide exchange on G proteins. Using this method, lithium was recently demonstrated to inhibit the coupling of both muscarinic cholinergic and beta-adrenergic receptors to pertussis toxin-sensitive and cholera toxin-sensitive G proteins, respectively, thus suggesting alteration of the function of G protein by lithium, as the single site for both the antimanic and antidepressant effects of this drug. One of the most puzzling aspects of the ability of lithium to ameliorate the manic-depressive condition is its relatively selective action upon the central nervous system (CNS). It was previously shown that lithium selectively attenuated the function of Gs proteins in the CNS. In the present study, we show that inhibition by lithium of muscarinic receptor-coupled G protein function is also selective to the CNS. The clinical profile of lithium, carbamazepine, and electroconvulsive treatment (ECT), agents that are effective in the prevention and treatment of bipolar affective disorder, differs from that of purely antidepressant drugs. Antidepressant drugs are effective in the acute treatment and prevention of depression only, and can even precipitate hypomanic or manic "switches," or "rapid cycling" between mania and depression. We have investigated and compared the effects of chronic antibipolar and antidepressant treatments on receptor-coupled G protein function. Antibipolar treatments (lithium, carbamazepine, ECT) attenuate both receptor-coupled Gs and non-Gs (i.e., Gi, Go) proteins function; in contrast, only Gs protein function is inhibited by antidepressant drugs [either tricyclics or monoamine oxidase (MAO) inhibitors]. Moreover, an integral adrenergic neuronal system is required for antidepressant inhibition of Gs protein function, as pretreatment with the noradrenergic neurotoxin DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) specifically abolishes the effects of antidepressant drugs on Gs protein, whereas antibipolar drug effects on G protein function are unaffected by DSP-4. Our results suggest that attenuation of beta-adrenergic receptor-coupled Gs protein function, which is common to both antidepressant and antibipolar treatments, may be the mechanism underlying their antidepressant therapeutic efficacy.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ziskind-Somerfeld research Award. The involvement of guanine nucleotide binding proteins in the pathogenesis and treatment of affective disorders. 158 23

The Nb2 node lymphoma cell line has been widely used as a model for investigating lactogen cellular actions. Both pertussis (PTX) and cholera (CTX) toxins modulate lactogen-stimulated Nb2 cell mitogenesis, suggesting G protein involvement in lactogen signal transduction. The following studies were performed to further investigate this possibility. Both PTX-sensitive (41 kDa) and CTX-sensitive substrates (42 and 45 kDa) were identified in Nb2 cell membrane and recognized by specific anti-Gi and anti-Gs antibodies, respectively. Equal numbers of Nb2 cells were then incubated with the lactogen human growth hormone (hGH, 10 ng/ml) for 0-72 h. Membrane protein prepared from each time point (50 micrograms) was compared in toxin-stimulated ADP-ribosylation studies. CTX-stimulated ADP-ribosylation was unaffected by prior hGH incubation. PTX-stimulated ADP-ribosylation increased 237 +/- 69% (X +/- S.E.) compared with 0-h controls (n = 11; p less than 0.01) after 4-7 h of hGH incubation then decreased toward 0-h samples by 24 and 72 h. No change in Gi alpha concentration was observed, but beta subunit concentration increased (145 +/- 14% at 7 h; p less than 0.01; n = 3) in a time course that paralleled the changes in PTX-stimulated ADP-ribosylation. In summary, 1) both Gi and Gs were present in Nb2 cell membrane, 2) incubation of cells with a lactogen, hGH, for 4-7 h markedly enhanced PTX-stimulated ADP-ribosylation of Gi alpha in vitro, whereas CTX-stimulated ADP-ribosylation of Gs alpha was unchanged, and 3) although no change in Gi alpha concentration was observed, beta subunit concentration increased in parallel with the increase in PTX-stimulated ADP-ribosylation of Gi alpha. These results suggest that hGH may modify PTX-stimulated ADP-ribosylation of Gi not by changing Gi alpha concentration, perhaps by increasing beta subunit concentration, enhancing association of Gi alpha by beta gamma subunits, which, in turn, is preferentially ADP-ribosylated. This may represent a late signal transduction event and may also have implications for other effectors dependent on Gi-mediated events.
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PMID:Human growth hormone enhances pertussis toxin-stimulated ADP-ribosylation of Gi in Nb2 cell membrane. 158 39

The activities of GTP-binding and GTPase in Candida albicans were present in the cytosol, KCl- and cholate-extractable fractions. At least two kinds of GTP-binding proteins were found in the cytosolic fraction; the major one with a molecular mass of about 30 kDa and the other about 500 kDa. The former specifically bound guanine nucleotides and was most likely to bind GDP since guanosine 5'-O-(thio) triphosphate (GTP gamma S)-binding was accelerated by addition of (NH4)2SO4. The latter showed no specificity in nucleotide binding and could also bind adenine nucleotides. The proteins were not ADP-ribosylated by either pertussis toxin or cholera toxin. These results indicate that ras-like monomeric, low molecular mass GTP-binding proteins distinct from heterotrimeric G proteins such as Gi, Go and Gs are present in C. albicans.
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PMID:Occurrence and biochemical characterization of GTP-binding proteins in Candida albicans. 158 60

Changes in beta-adrenoceptors, GTP binding (G) proteins and adenylate cyclase (AC) activity of ventral prostates of rats during aging were studied in these experiments. The density of beta-adrenoceptors increased markedly after birth, reaching a maximum in the tissues at 16 weeks of age and remained at this level for about 90 weeks. When stimulated by isoproterenol, the AC activity increased 4- and 22-fold in 2- and 8-week-old rats, respectively, but only 7-fold in both 16- and 104-week-old rats. Activation of AC by forskolin was the greatest during the 2 weeks after birth and then showed a sharp decrease, reaching a plateau in the tissues at 8 weeks. Bmax value of [35S]GTP gamma S binding to the tissues was the largest at 8 weeks. Pretreatment of the tissues with pertussis or cholera toxin caused age-dependent changes in both the binding abilities of Gi and Gs proteins to GTP that coincided with changes in the binding of G proteins to GTP. There was no difference between the abilities of Gi and Gs proteins to bind to GTP in the tissues of rats of the respective age. These results show that changes in the binding ability of G proteins to GTP influence the function of ventral prostates of rats during the aging process, and this is mediated through the regulation of AC activity.
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PMID:[Age-dependent changes in the adenylate cyclase system of rat ventral prostate]. 159 16

Changes in cytosolic calcium concentration ([Ca2+]i) in response to extracellular calcium and epinephrine were monitored in individual rat adipocytes by both photon counting and digital imaging techniques utilizing the intracellular fluorescent calcium probes Fura-2 and Indo-1. Adipocytes containing Fura-2 were attached to coverslips and shown to be as hormonally responsive to insulin as adipocytes in suspension [3.5 +/- 0.8 (n = 5) vs. 4.2 +/- 0.6 (n = 8)-fold increase in glucose oxidation over basal in response to 0.7 nM insulin]. Basal [Ca2+]i in single rat adipocytes was found to be 128 +/- 6 nM (n = 100). The addition of either extracellular calcium or epinephrine elicited transient, concentration-dependent increases in [Ca2+]i. Although the characteristics of calcium- and epinephrine-induced calcium transients are generally similar, the peak [Ca2+]i increase over basal is higher in response to calcium vs. epinephrine [37 and 64% (1 and 27 microM epinephrine), vs. 132 and 236% (2 and 4 mM calcium)]. All the cells tested responded to calcium but only 67% responded to epinephrine. Both alpha- and beta-adrenergic agonists were able to increase [Ca2+]i. The epinephrine-induced [Ca2+]i transients appear to be dependent upon extra-cellular calcium. Neither cholera nor pertussis toxin treatments altered basal [Ca2+]i. However, after treatment of adipocytes with either pertussis or cholera toxin, epinephrine stimulated oscillations in [Ca2+]i. Digital imaging revealed that adipocytes demonstrate a high degree of intracellular spatial heterogeneity and intercellular variability in the magnitude of response to both calcium and epinephrine. These studies demonstrate the feasibility of using single rat adipocytes to monitor intracellular free calcium, using both photon counting and digital imaging.
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PMID:The effects of extracellular calcium and epinephrine on cytosolic-free calcium in single rat adipocytes. 159 65

The mRNA level of the type-1 angiotensin II receptor (AT1) was down-regulated by angiotensin II in cultured rat glomerular mesangial cells. The effect was maximum with 1 microM AII at 6 h, sensitive to cycloheximide, and specific to AT1 since this phenomenon was blocked by DuP753, an AT1 antagonist, but not by type-2 antagonist PD123319. Dibutyryl cAMP, forskolin, and cholera toxin also caused AT1 down-regulation. These effects were not altered by either the protein kinase A inhibitor H-8 or cycloheximide. Calcium ionophore A23187, pertussis toxin, protein kinase C inhibitor staurosporine, or prolonged incubation with phorbol ester were without effect. These results suggest that there are at least two pathways to down-regulate AT1 mRNA; one way is an angiotensin II-induced, protein kinase C-independent, and cycloheximide-sensitive pathway and the other is an angiotensin II-independent, cAMP-induced, and cycloheximide-insensitive pathway.
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PMID:Two distinct pathways in the down-regulation of type-1 angiotension II receptor gene in rat glomerular mesangial cells. 159 49

The GTP-binding proteins on luminal and basolateral membrane vesicles from outer cortex (pars convoluta) and outer medulla (pars recta) of rabbit proximal tubule have been examined. The membrane vesicles were highly purified, as ascertained by electron microscopy, by measurements of marker enzymes, and by investigating segmental-specific transport systems. The [35S]GTP gamma S binding to vesicles, and to sodium cholate-extracted proteins from vesicles, indicated that the total content of GTP-binding proteins were equally distributed on pars convoluta, pars recta luminal and basolateral membranes. The membranes were ADP-ribosylated with [32P]NAD+ in the presence of pertussis toxin and cholera toxin. Gel electrophoresis revealed, for all preparations, the presence of cholera toxin [32P]ADP-ribosylated 42 and 45 kDa G alpha s proteins, and pertussis toxin [32P]ADP-ribosylated 41 kDa G alpha i1, 40 kDa G alpha i2 and 41 kDa G alpha i3 proteins. The 2D electrophoresis indicated that Go's were not present in luminal nor in basolateral membranes of pars convoluta or pars recta of rabbit proximal tubule.
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PMID:GTP-binding proteins in luminal and basolateral membranes from pars convoluta and pars recta of rabbit kidney proximal tubule. 161 19


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