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 basis for the hypersensitive response of glycogen phosphorylase to epinephrine stimulation was investigated in adult rat cardiomyocytes isolated from normal and alloxan-diabetic animals. To assess potential G-protein involvement in the response, normal and diabetic derived myocytes were incubated with either cholera or pertussis toxin prior to hormonal stimulation. Pretreatment of cardiomyocytes with cholera toxin resulted in a potentiated response to epinephrine stimulation whereas pertussis toxin did not affect the activation of this signaling pathway. To determine if the enhanced response of phosphorylase activation resulted from an alteration in adenylate cyclase activation, the cells were challenged with forskolin. After 3 hr in primary culture, diabetic cardiomyocytes exhibited a hypersensitive response to forskolin stimulation relative to normal cells. However, after 24 hr in culture, both normal and diabetic myocytes responded identically to forskolin challenge. The present data suggest that a cholera toxin sensitive G-protein mediates the hypersensitive response of glycogen phosphorylase to catecholamine stimulation in diabetic cardiomyocytes and this response which is present in alloxan-diabetic cells and is induced in vitro in normal cardiomyocytes is primarily due to a defect at a post-receptor site.
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PMID:Post-receptor defect accounts for phosphorylase hypersensitivity in cultured diabetic cardiomyocytes. 148 Jan 65

Previous studies from our laboratory have suggested that diabetes-associated central nervous system abnormalities are characterized by progressive alterations of neurotransmitters and of transductional Gi/Go proteins. In this study, we have further characterized these abnormalities in the striatum of alloxan-diabetic rats by means of adenosine 5'-diphosphate (ADP)-ribosylation, and Western and Northern blotting techniques. Fourteen weeks after diabetes induction, pertussis-toxin (PTX) catalyzed ADP-ribosylation of Gi/Go proteins was markedly reduced in diabetic animals, as shown by a clear decrease of 32P-ADPribose incorporation into G protein alpha subunits. In agreement with our previous pharmacological studies that showed a reduction of Gi-mediated modulation of adenylate cyclase activity only at this stage of diabetes, no changes in PTX-mediated ADP-ribosylation were observed earlier (5-wk diabetes). Immunoblotting studies performed by using antibodies selectively raised against Gi-2, Go, and Gs proteins did not reveal any differences between control and diabetic animals at any stage of diabetes. Similarly, the mRNAs corresponding to the alpha subunits of Gi-2, Go, and Gs proteins did not show any marked changes in chronic diabetic rats with respect to control animals. It is therefore concluded that diabetes is associated with development of a time-related alteration of cerebral Gi/Go proteins and that this defect is not owing to gross changes in either content of G proteins or mRNA level, but probably reflects modifications of G protein's structure or physiological status affecting the coupling with membrane effector systems and the sensitivity to PTX.
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PMID:Diabetes-induced alterations of central nervous system G proteins. ADP-ribosylation, immunoreactivity, and gene-expression studies in rat striatum. 149 84

The early alterations of G-protein-dependent transductional mechanisms have been characterized in the retina of alloxan-treated diabetic rats. Five weeks after alloxan injection, pertussis toxin radiolabeling of Gi/Go proteins was markedly reduced in the retina of diabetic animals, suggesting either a reduced expression and/or the presence of some structural modification of these G-protein subtypes. The functional activity of Gs proteins, measured as stimulation of membrane adenylate cyclase by dopamine, did not seem to be impaired at this stage of the pathology; basal adenylate cyclase activity was indeed increased in diabetic rats, consistent with the observed reduction of Gi/Go inhibitory proteins. Such functional alterations of the cAMP producing system were causally related to diabetes induction, since they were reversed by treatment of diabetic animals with insulin. These results suggest that G-protein dependent transduction mechanisms are altered in the retina of diabetic animals, and that a defect of Gi/Go proteins could represent an early transductional damage in the development of diabetic retinopathy.
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PMID:Early alterations of Gi/Go protein-dependent transductional processes in the retina of diabetic animals. 165 57

Hepatocyte membranes from both lean and obese Zucker rats exhibited adenylate cyclase activity that could be stimulated by glucagon, forskolin, NaF and elevated concentrations of p[NH]ppG. In membranes from lean animals, functional Gi was detected by the ability of low concentrations of p[NH]ppG to inhibit forskolin-activated adenylate cyclase. This activity was abolished by treatment of hepatocytes with either pertussis toxin or the phorbol ester TPA, prior to making membranes for assay of adenylate cyclase activity. In hepatocyte membranes from obese animals no functional Gi activity was detected. Quantitative immunoblotting, using an antibody able to detect the alpha subunit of Gi, showed that hepatocyte plasma membranes from both lean and obese Zucker rats had similar amounts of Gi-alpha subunit. This was 6.2 pmol/mg plasma membrane for lean and 6.5 pmol/mg plasma membrane for obese animals. Using thiol pre-activated pertussis toxin and [32P]-NAD+, similar degrees of labelling of the 40 kDa alpha subunit of Gi were found using plasma membranes of both lean and obese Zucker rats. We suggest that liver plasma membranes from obese Zucker rats express an inactive Gi alpha subunit. Thus lesions in liver Gi functioning are seen in insulin-resistant obese rats and in alloxan- and streptozotocin-induced diabetic rats which also show resistance as regards the acute actions of insulin. Liver plasma membranes of obese animals also showed an impairment in the coupling of glucagon receptors to Gs-controlled adenylate cyclase, with the Kd values for activation by glucagon being 17.3 and 126 nM for lean and obese animals respectively. Membranes from obese animals also showed a reduced ability for high concentration of p[NH]ppG to activate adenylate cyclase. The use of [32P]-NAD+ and thiol-preactivated cholera toxin to label the 43 kDa and 52 kDa forms of the alpha-subunit of Gs showed that a reduced labelling occurred using liver plasma membranes from obese animals. It is suggested that abnormalities in the levels of expression of primarily the 52 kDa form of alpha-Gs may give rise to the abnormal coupling between glucagon receptors and adenylate cyclase in liver membranes from obese (fa/fa) Zucker rats.
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PMID:Multiple defects occur in the guanine nucleotide regulatory protein system in liver plasma membranes of obese (fa/fa) but not lean (Fa/Fa) Zucker rats: loss of functional Gi and abnormal Gs function. 256 40

Mice were infected intranasally with a sub-lethal dose of Bordetella pertussis organisms (1.2 x 10(5) colony forming units per mouse), control animals receiving the vehicle intranasally. The experiments were performed 14 days later. Serum glucose and insulin concentrations were studied across a 24 h period in freely fed animals and the changes in serum glucose and insulin concentrations in response to feeding were examined in mice fasted for 18 h. The responsiveness of mice to injected insulin (0.5 and 5.0 units/kg i.v.) was also examined. Pertussis-infected mice developed hypoglycaemia and hyperinsulinaemia relative to the controls. These changes were present across a 24 h period although the magnitude of the differences between values seen in control and infected animals varied and the hyperinsulinaemia was not seen at all times. Infected mice showed a markedly diminished hyperglycaemia and an exaggerated hyperinsulinaemia following food ingestion, relative to normal controls. Pertussis-induced hypoglycaemia was abolished following destruction of the pancreatic islet B cells with alloxan (80 mg/kg i.v.). The serum glucose response to a low dose of insulin was significantly attenuated by B. pertussis infection although the hypoglycaemia produced by a high dose was prolonged. It was concluded that B. pertussis infection-induced hypoglycaemia was secondary to hyperinsulinaemia, possibly caused by an exaggerated insulin secretory response to food intake.
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PMID:Role of insulin in the hypoglycaemic effect of sublethal Bordetella pertussis infection in mice. 351 82

Intranasal infection of mice with a sublethal dose of Bordetella pertussis produced hypoglycaemia and hyperinsulinaemia. Exposure to ether vapour did not modify serum insulin concentrations in control mice, but produced a marked transient hyperinsulinaemia in mice infected with B. pertussis. A similar hyperinsulinaemia in infected, but not control, mice was also seen after a brief (10-15 s) period of anoxia (produced by exposure to an atmosphere of 100% N2 or 100% CO2), or following the injection of histamine or 2-deoxyglucose. Exposure to cold (2-4 degrees C) or hypoxia (8% O2 in 92% N2), however, did not alter serum concentrations of insulin in control or infected mice. The hyperinsulinaemic response to ether stress observed in mice infected with B. pertussis was abolished by pretreatment with alloxan. The hyperglycaemic effects of histamine and 2-deoxyglucose were attenuated or abolished in mice infected with B. pertussis. However, none of the stimuli which produced hyperinsulinaemia in the infected mice resulted in any further lowering of the blood glucose concentration. Pretreatment of mice with pertussis toxin (150 ng/mouse, i.v.) produced hypoglycaemia similar in magnitude to that found in animals infected with B. pertussis. Moreover, exposure of mice treated with pertussis toxin to ether vapour produced marked hyperinsulinaemia. It is suggested that the metabolic alterations seen in animals infected with B. pertussis may be mediated by pertussis toxin.
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PMID:Hypoglycaemia and acute stress-induced hyperinsulinaemia in mice infected with Bordetella pertussis or treated with pertussis toxin. 354 69

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

In order to gain insight into the antioxidant effect of the cell extract from Bordetella pertussis (strain 18-323, phase I) pancreatic antioxidant enzymes, glutathione (GSH), lipid conjugated dienes, DNA strand breaks in islet cells and the in vitro ROM scavenging potential of the extract were studied in 18 hr-fasted mice after administration (i.v.) of the extract (1 mg/kg body wt) 1 hr before alloxan treatment. The antioxidant enzymes activities as well as the glutathione content, which were severely depleted in the alloxan group, were found to be significantly restored in the extract treated group at the end of 48 hr. Moreover, the extract arrested the two-fold increase in lipid conjugated dienes, the primary products of lipid peroxidation, and afforded significant protection against DNA strand breakage in islet cells of pancreas in alloxan diabetic mice. In addition, it caused a six-fold increase in serum insulin levels of normal mice in 15 min and also demonstrated an unique in vitro superoxide anion radical scavenging activity at a dose of 37.5 micrograms/ml in 10 min. B. pertussis extract thus appears to exert its antioxidant protection through stimulation of insulin release from pancreas and hitherto unobserved intrinsic superoxide anion radical scavenging ability.
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PMID:Mechanism of the antioxidant effect of Bordetella pertussis extract. 785 40

X-ray microanalysis was used to investigate whether cAMP- and/or Ca2+-activated regulation of chloride and potassium efflux is expressed in primary cultures of sweat gland duct cells. The effects of extracellular UTP and ATP on the duct cells, and the signalling system involved in the response to ATP was also studied. Primary cultures from duct cells of human sweat glands responded to 1 microM carbachol, 2 microM of the Ca2+ ionophore A23187, or 5 mM 8-bromo-cAMP stimulation for 5 min, resulting in a decrease in cellular Cl and K concentrations. 50 microM 5-nitro-2-(3-phenylpropyl-amino)-benzoic acid (NPPB), a Cl- channel blocker, can inhibit the decrease in Cl concentration induced by cAMP. Extracellular (200 microM) ATP caused a decrease of Cl and K in cultured duct cells, while (200 microM and 2 mM) UTP was ineffective. Both the phosphoinositidase C inhibitor U73122 (10 microM) and the absence of extracellular Ca2+ abolished the ATP-induced decrease in Cl and K content. Alloxan (1.25 mM), an adenylate cyclase inhibitor, had an inhibitory effect on the response to ATP. The decrease in K, but not in Cl, content in the cells elicited by ATP was blocked by prior incubation with 100 ng/ml pertussis toxin, indicating the coupling of ATP to pertussis toxin-sensitive G-proteins. In conclusion, both Ca2+- and cAMP-dependent Cl- permeability is present in primary cultures from duct cells of human sweat gland. The response to ATP can be mediated both by Ca2+- and by cAMP-dependent pathways, and is coupled to pertussis toxin-sensitive G-proteins.
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PMID:Regulation of ion content in primary cultures from reabsorptive ducts of human sweat glands studied by X-ray microanalysis. 987 64

Extracellular ATP and UTP can increase membrane permeability in the sweat gland, but the intracellular signalling regulating the response to these agonists is poorly understood. Stimulation of Cl- transport by nucleotides has been suggested as a pharmacological therapy to improve Cl- secretion in patients with cystic fibrosis. In the present study, regulation of Na+, Cl- and K+ transport in primary cultures of cells from the secretory coil of human sweat glands was investigated by electron probe X-ray microanalysis. Stimulation with 200 microM UTP for 2 min at room temperature caused a significant increase in intracellular Na but did not affect Cl and K. After 5 min, the Na concentration was still increased, but now also a significant decrease in Cl and K was observed, indicating an increase in Cl- and K+ permeability. The effect of UTP on Cl- secretion was enhanced in Mg2+-deficient buffer, indicating that the response is elicited by the extracellular fully ionized form of UTP (UTP4+), but not by MgUTP2+. The effects of UTP were abolished in Ca2+-deficient buffer supplemented with EGTA. Alloxan, an adenylate cyclase inhibitor, did not inhibit the response to UTP. These results indicate that the membrane Cl- and K+ permeability elicited by UTP in primary coil cell cultures is Ca2+-dependent. The response to UTP did not attenuate at 8 degrees C, suggesting that it could be activated, in part, via ligand-gated ion channels. The effect of UTP was not decreased in the presence of ouabain. Pre-treatment of the cells with pertussis toxin (24 h) had minor effects on Cl- secretion activated by UTP, indicating a role for G proteins in the UTP activation of Cl- secretion.
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PMID:Effects of UTP on Na+, Cl- and K+ transport in primary cultures from human sweat gland coils. 1019 72


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