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)

Cholera toxin and other heat-labile enterotoxins have the same subunit structure (A5B) and all catalyse the mono ADP-ribosylation of Ns, a regulator of adenylate cyclase, probably at an arginine residue. They also ADP-ribosylate a variety of other membrane and soluble proteins at much slower rates. The rates differ from protein to protein but it may be that every arginine residue in every protein is ADP-ribosylated at some slow rate. A guanine nucleotide triphosphate is required for the ADP-ribosylation of the major (Ns) and minor substrates alike. It used to be thought that all the substrates were GTP-binding proteins but this cannot be so. Rather, the GTP is required because it has to bind to some additional site on the membrane, termed 'S', in a cooperative event that involves a soluble protein called cytosolic factor (CF). If we expose erythrocyte membranes to CF and the GTP analogue Gpp(NH)p we can later extract in detergent a factor or complex that confers upon naive erythrocyte membranes the ability to be ADP-ribosylated. Pertussis toxin also has an A5B structure and acts on an intracellular substrate for ADP-ribosylation, namely the negative regulator of adenylate cyclase, called Ni. ADP-ribosylation prevents the reduction of cyclase activity by inhibitory hormones. The ADP-ribosylation of Ns or Ni does not affect the rate of ADP-ribosylation of the other protein.
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PMID:Toxins which activate adenylate cyclase. 384 38

Hydroxylamine stability has been used to classify (ADP-ribose)protein bonds into sensitive and resistant linkages, with the former representing (ADP-ribose)glutamate, and the latter, (ADP-ribose)arginine. Recently, it was shown that cysteine also serves as an ADP-ribose acceptor. The hydroxylamine stability of [cysteine([32P]ADP-ribose)]protein and [arginine([32P] ADP-ribose)]protein bonds was compared. In transducin, pertussis toxin catalyzes the ADP-ribosylation of a cysteine residue, whereas choleragen (cholera toxin) modifies an arginine moiety. The (ADP-ribose)cysteine bond formed by pertussis toxin was more stable to hydroxylamine than was the (ADP-ribose)arginine bond formed by choleragen. The (ADP-ribose)cysteine bond apparently represents a third class of ADP-ribose bonds. Pertussis toxin ADP-ribosylates the inhibitory guanyl nucleotide-binding regulatory protein (Gi) of adenylate cyclase, whereas choleragen modifies the stimulatory guanyl nucleotide-binding regulatory protein (Gs). These (ADP-ribose)protein linkages are identical in stability to those formed in transducin by the two toxins, consistent with the probability that cysteine and arginine are modified in Gi and Gs, respectively. Bonds exhibiting differences in hydroxylamine-stability were found in membranes from various non-intoxicated mammalian cells following incubation with [32P]NAD, which may reflect the presence of endogenous NAD:protein-ADP-ribosyl-transferases.
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PMID:Amino acid-specific ADP-ribosylation. Sensitivity to hydroxylamine of [cysteine(ADP-ribose)]protein and [arginine(ADP-ribose)]protein linkages. 393 72

The intermediary role of the putative inhibitory regulatory membrane protein "Ni" in the "antigonadal" activity of the neurohypophysial hormones was investigated in vitro with the use of a primary culture of rat testicular cells. To this end, use was made of the pertussis toxin (PT) probe, an exotoxin of Bordetella pertussis presumed to modify and inactivate a membrane protein related to or identical with Ni. Testicular cells were pretreated with PT (70 ng/ml) for 24 h, a duration of exposure known to result in a maximal PT effect. Thereafter, the cells were cultured for an additional 48 h in the absence or presence of hCG (10 ng/ml), with or without a maximal inhibitory dose (10(-6) M) of the neurohypophysial principle arginine vasotocin (AVT). Although concomitant treatment of control cells with AVT produced a profound (95%) inhibition of hCG-stimulated testosterone accumulation, PT pretreatment resulted in a long-lasting (greater than 4 days) abolition of this "antigonadal" effect. Furthermore, pretreatment with PT resulted in significant (P less than 0.05) augmentation of the hCG-stimulated accumulation of extracellular cAMP (1.5- to 2.0-fold) and testosterone (1.7- to 3.8-fold), presumably as a result of abolition of the "basal" tonic inhibition of adenylate cyclase activity. Taken together, these findings constitute the first demonstration of the involvement of Ni in the "antigonadal" activity of the neurohypophysial hormones and in the regulation of testicular function, thereby raising the intriguing possibility that testicular Ni may serve as the coupling unit of inhibitory receptors other than those for the neurohypophysial hormones, integrating varied incoming signals of endocrine, paracrine or autocrine nature.
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PMID:"Antigonadal" activity of the neurohypophysial hormones in cultured rat testicular cells: abolition by pertussis toxin. 608 80

Pancreatic islets were maintained in culture with or without islet-activating protein (IAP), which is a new protein purified from culture medium of Bordetella pertussis. These cultured islets (IAP-treated or control) were then incubated for 30 min in IAP-free medium with various insulin secretagogues. During incubation, much more insulin was released from IAP-treated islets than control islets in response to glucose, arginine, glucagon, and sulfonylurea. IAP was effective in this regard when added to cultures at concentrations higher than 0.01 ng/ml; the effect was dependent on concentration up to 100 ng/ml. Enhanced insulin secretion was associated with accumulation of cyclic AMP when breakdown of the nucleotide was prevented by a methylxanthine. Epinephrine caused marked inhibitions, via alpha-adrenergic receptors, of glucose-induced insulin release, cyclic AMP accumulation and 45Ca uptake in control islets but did not in IAP-treated islets during incubation. None of these effects of IAP pretreatment were observed unless the medium for incubation was supplemented with Ca ions. 45Ca ion flux through the islet cell membrane was accelerated by the IAP treatment; conceivably, IAP was effective in causing sustained activation of native calcium ionophores on the membrane, which would be responsible for the enhanced insulin and cyclic AMP responses characteristic of IAP-treated islets.
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PMID:In vitro effects of islet-activating protein on cultured rat pancreatic islets. Enhancement of insulin secretion, adenosine 3':5'-monophosphate accumulation and 45Ca flux. 616 8

Pertussis toxin (islet-activating protein) activates adenylate cyclase in susceptible cells by ADP-ribosylating an inhibitory component of the cyclase system. This toxin, assayed in a cell-free system in the presence of high concentrations of thiol, catalyzed the hydrolysis of NAD to ADP-ribose and nicotinamide. This NAD glycohydrolase activity co-chromatographed on Sephacryl G-200 in 6.5 M urea, pH 3.2, 0.1 M glycine with the ADP-ribosyltransferase activity of the toxin, as monitored by the transfer of [32P]ADP-ribose from [32P]NAD to a 41,000-Da protein in NG108-15 neuroblastoma X glioma hybrid cells. In the absence of thiol, the native holotoxin was enzymatically inactive. Following addition of 250 mM dithiothreitol to the assay, maximal enzymatic activity was evident after a delay of approximately 1 h; with 20 mM thiol, the delay was longer. The Km for NAD with the fully activated enzyme was 25 microM; the Km did not appear to vary with the extent of activation. Thiol was necessary in a cell-free system to demonstrate NAD glycohydrolase activity. When extensively washed membranes were used as a source of 41,000-Da substrate, thiol was necessary to observe ADP-ribosylation in some cases (human erythrocytes) and significantly stimulated activity in others (NG108-15 cells). In contrast to the bacterial toxins choleragen and Escherichia coli heat-labile enterotoxin that ADP-ribosylate stimulatory components of the cyclase system, pertussis toxin did not transfer ADP-ribose to low molecular weight guanidino compounds, such as arginine or agmatine.
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PMID:Activation by thiol of the latent NAD glycohydrolase and ADP-ribosyltransferase activities of Bordetella pertussis toxin (islet-activating protein). 631 27

The effect of Bordetella pertussis vaccine on plasma glucose, insulin and glucagon secretion was investigated in normal and alloxan dogs. On the 8th day after the vaccine injection, in normal and alloxan dogs during the infusion of arginine and glucose, the plasma glucose level was lower and the IRI level was higher than in the saline controls. On the other hand, the plasma IRG level showed no significant alloxan dogs this vaccine made the plasma IRG level lower during arginine infusion than in the saline controls and suppressed it significantly during glucose infusion. These effects of the vaccine disappeared on the 30th day after its injection into normal and alloxan dogs. It is suggested that in normal dogs Bordetella pertussis vaccine decreased plasma glucose through the promotion of insulin secretion without any effect on glucagon secretion, while in alloxan dogs this vaccine might alleviate hyperglycemia through the enhancement of insulin and the inhibition of glucagon secretion.
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PMID:Effect of Bordetella pertussis vaccine on glucagon secretion in normal and alloxan dogs. 701 12

A new protein termed islet-activating protein (IAP) has recently been extracted from the culture medium of Bordetella pertussis, and shown to enhance insulin secretion in vivo in rats or in vitro in isolated pancreatic islets due to activation of native calcium ionophores. However, it has not been clarified whether or not IAP enhances the secretion of insulin in human pancreatic islets. In order to examine the effect of IAP on human pancreatic islets, pancreatic tissues were obtained from seven patients who had appeared normal in a glucose tolerance test prior to pancreatectomy. Insulin secretion was significantly increased in IAP treated pancreatic islets by the glucose and the arginine stimuli. It is concluded that IAP enhances the insulin secretion in response to insulin secretagogues in human pancreatic islets, suggesting the possible clinical application of IAP to diabetic patients.
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PMID:Effect of islet-activating protein (IAP) upon insulin secretion from human pancreatic islets. 703 Jul 21

The mechanism of morphologic change of human cultured umbilical vein endothelial cells (HUVECs) caused by fibrin was investigated. Ancrod, a thrombin-like enzyme, did not cause morphologic alteration of HUVEC by itself at concentrations ranging from 0.01 to 10 U/ml. However, when 0.02 U/ml of ancrod was added to cultured HUVEC monolayers in the presence of citrated plasma, it caused pronounced morphologic change of HUVEC after 6-10 h incubation period. Gly-Pro-Arg-Pro (4 mg/ml), an inhibitor of fibrin polymerization, prevented the morphologic alteration, indicating that the morphologic alteration was caused by the polymerized fibrin. The morphologic change of HUVEC caused by ancrod-generated fibrin was not observed in the presence of an intracellular calcium mobilization inhibitor TMB-8 (50 microM), and the morphologic alteration was also less pronounced with BAPTA(15 microM)-loaded HUVECs and HUVECs pretreated with EGTA (1.2 mM). Ancrod (in Medium 199) itself did not stimulate phosphoinositide breakdown of HUVEC. However, when ancrod was present in plasma, it caused an increase of [3H]IP1 of HUVECs preloaded with [3H]myoinositol. This IP1 increment was inhibited by Gly-Pro-Arg-Pro. The increase of IP1 was significantly inhibited by the pretreatment of monoclonal antibodies 23C6 and 7E3 directed against alpha v beta 3 integrin. Neomycin (1 mM) and pertussis toxin (100 ng/ml), but not aspirin or mepacrine, blocked this enhanced phosphoinositide breakdown. The morphologic change was also prevented by the monoclonal antibodies, 23C6 and 7E3. These results suggest that both intra- and extra-cellular calcium participate in the event of morphologic change of HUVEC caused by ancrod-generated fibrin, and the morphologic change is mediated, at least in part, by fibrin binding to integrin alpha v beta 3 on HUVECs, causing the subsequent activation of the endogenous G-protein coupled phospholipase C.
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PMID:The morphologic change of endothelial cells by ancrod-generated fibrin is triggered by alpha v beta 3 integrin binding and the subsequent activation of a G-protein coupled phospholipase C. 748 43

Bordetella pertussis releases a specific peptidoglycan fragment known as tracheal cytotoxin (TCT) that reproduces the respiratory epithelial cytopathology of whooping cough (pertussis). In vitro, TCT inhibits DNA synthesis in hamster trachea epithelial cells and causes specific destruction of ciliated cells in explants of human and hamster respiratory epithelium. We have recently demonstrated that TCT triggers production of intracellular interleukin 1 by respiratory epithelial cells, and this cytokine may act as an intermediate signal in the generation of TCT toxicity. Here we report the identification of a subsequent critical step in this pathway: induction of nitric oxide synthesis in the respiratory epithelium. The toxic effects of nitric oxide are consistent with spectroscopic evidence of the formation of iron-dinitrosyl-dithiolate complexes in TCT-treated cells. Aconitase, with its iron-sulfur center, is one expected target of nitric oxide, and TCT inhibited 80% of the activity of this enzyme in respiratory epithelial cells. The deleterious effects of TCT and interleukin 1 were dramatically attenuated by the nitric oxide synthase inhibitors NG-monomethyl-L-arginine and aminoguanidine. These results indicate that nitric oxide mediates the toxicity of TCT for the respiratory epithelium, thus implicating a central role for nitric oxide in the pathogenesis of pertussis.
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PMID:Epithelial autotoxicity of nitric oxide: role in the respiratory cytopathology of pertussis. 750 15

Plasma membranes isolated from dispersed gastric muscle cells exhibited calmodulin-dependent NOS activity that was stimulated by Ca2+ in the range 0.1-1 mM (maximum 10 microM). Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) (in the presence of GTP), and GTP gamma S (guanosine 5'-O-(gamma-thio)triphosphate) stimulated NOS activity in a concentration-dependent fashion above that maximally stimulated by Ca2+. The increase in NOS activity induced by VIP, PACAP, and GTP gamma S was abolished by GDP beta S (guanosine 5'-O-(beta-thio)diphosphate), which had no effect on NOS activity stimulated by Ca2+. The NOS inhibitor NG-nitro-L-arginine and the calmodulin antagonist calmidazolium abolished NOS activity stimulated by all agents including Ca2+. NOS activity stimulated by GTP gamma S, VIP, and PACAP was inhibited by Gi alpha 1-2 antibody but not by Gq alpha, Gs alpha, and Gi alpha 3 antibodies. NOS activity stimulated by VIP and PACAP was inhibited by 80-83% in membranes derived from pertussis toxin-treated cells. We conclude that a Ca2+/calmodulin-dependent NOS present in plasma membranes of gastric muscle cells is activated by two homologous peptide transmitters, VIP and PACAP, via a common receptor coupled to pertussis toxin (PTx)-sensitive Gi1-2. The study provides the first evidence of receptor-mediated G protein activation of NOS in smooth muscle cells.
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PMID:Vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide-dependent activation of membrane-bound NO synthase in smooth muscle mediated by pertussis toxin-sensitive Gi1-2. 751 75


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