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)

Liver plasma membranes prepared from genetically diabetic (db/db) mice expressed levels of Gi alpha-2, Gi alpha-3 and G-protein beta-subunits that were reduced by some 75, 63 and 73% compared with levels seen in membranes from lean animals. In contrast, there were no significant differences in the expression of the 42 and 45 kDa forms of Gs alpha-subunits. Pertussis toxin-catalysed ADP-ribosylation of membranes from lean animals identified a single 41 kDa band whose labelling was reduced by some 86% in membranes from diabetic animals. Cholera toxin-catalysed ADP-ribosylation identified two forms of Gs alpha-subunits whose labelling was about 4-fold greater in membranes from diabetic animals compared with those from lean animals. Maximal stimulations of adenylyl cyclase activity by forskolin (100 microM), GTP (100 microM), p[NH]ppG (100 microM), NaF (10 mM) and glucagon (10 microM) were similar in membranes from lean and diabetic animals, whereas stimulation by isoprenaline (100 microM) was lower by about 22%. Lower concentrations (EC50-60 nM) of p[NH]ppG were needed to activate adenylyl cyclase in membranes from diabetic animals compared to those from lean animals (EC50-158 nM). As well as causing activation, p[NH]ppG was capable of eliciting a pertussis toxin-sensitive inhibitory effect upon forskolin-stimulated adenylyl cyclase activity in membranes from both lean and diabetic animals. However, maximal inhibition of adenylyl cyclase activity in membranes from diabetic animals was reduced to around 60% of that found using membranes from lean animals. Pertussis toxin-treatment in vivo enhanced maximal stimulation of adenylyl cyclase by glucagon, isoprenaline and p[NH]ppG through a process suggested to be mediated by the abolition of functional Gi activity. The lower levels of expression of G-protein beta-subunits, in membranes from diabetic compared with lean animals, is suggested to perturb the equilibria between holomeric and dissociated G-protein subunits. We suggest that this may explain both the enhanced sensitivity of adenylyl cyclase to stimulation by p[NH]ppG in membranes from diabetic animals and the altered ability of pertussis and cholera toxins to catalyse the ADP-ribosylation of G-proteins in membranes from these two animals.
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PMID:Determination of G-protein levels, ADP-ribosylation by cholera and pertussis toxins and the regulation of adenylyl cyclase activity in liver plasma membranes from lean and genetically diabetic (db/db) mice. 193 44

The possible involvement of a stimulatory guanosine triphosphate (GTP)-binding (G) protein in epidermal growth factor (EGF)-induced phosphoinositide hydrolysis has been investigated in permeabilized NIH-3T3 cells expressing the human EGF receptor. The mitogenic phospholipid lysophosphatidate (LPA), a potent inducer of phosphoinositide hydrolysis, was used as a control stimulus. In intact cells, pertussis toxin partially inhibits the LPA-induced formation of inositol phosphates, but has no effect on the response to EGF. In cells permeabilized with streptolysin-O, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) dramatically increases the initial rate of inositol phosphate formation induced by LPA. In contrast, activation of phospholipase C (PLC) by EGF occurs in a GTP-independent manner. Guanine 5'-O-(2-thiodiphosphate) (GDP beta S) which keeps G proteins in their inactive state, blocks the stimulation by LPA and GTP gamma S, but fails to affect the EGF-induced response. Tyrosine-containing substrate peptides, when added to permeabilized cells, inhibit EGF-induced phosphoinositide hydrolysis without interfering with the response to LPA and GTP gamma S. These data suggest that the EGF receptor does not utilize an intermediary G protein to activate PLC and that receptor-mediated activation of effector systems can be inhibited by exogenous substrate peptides.
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PMID:Epidermal growth factor-induced phosphoinositide hydrolysis in permeabilized 3T3 cells: lack of guanosine triphosphate dependence and inhibition by tyrosine-containing peptides. 196 91

The effect of the vasodilatory peptide bradykinin on the regulation of phosphoinositide metabolism in endothelial cells was investigated. Activation of phosphoinositide metabolism by bradykinin in the endothelium of the bovine pulmonary artery was not blocked by pertussis toxin, which ADP-ribosylates a membrane protein of molecular mass 40 kDa, but botulinum toxin, which ADP-ribosylates a membrane protein of molecular mass 24 kDa, fully blocked bradykinin-stimulated phosphoinositide metabolism. The effect of bradykinin was potentiated by guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S), an activator of GTP-binding proteins, and inhibited by guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S), an inhibitor of GTP-binding proteins. Activation of phosphoinositide metabolism by bradykinin was fully blocked by a B2-receptor antagonist, whereas a B1-receptor antagonist did not affect bradykinin action. It is concluded that the B2-receptor in endothelial cells is coupled to phospholipase C via a GTP-binding protein, which is a substrate for botulinum toxin.
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PMID:Regulation by bradykinin of phosphoinositide metabolism in the endothelial cells of the pulmonary artery. 196 71

Somatostatin inhibited Ca2(+)-induced insulin secretion in permeabilized HIT-T15 cells, albeit with decreased sensitivity relative to intact cells. The inhibitory action required the presence of GTP, whereas GDP could not substitute for GTP. Pertussis-toxin treatment before cell permeabilization abolished the inhibition of secretion. Thus somatostatin, by activating a G-protein, interferes with exocytosis distal to the generation of soluble intracellular messengers.
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PMID:Somatostatin inhibition of Ca2(+)-induced insulin secretion in permeabilized HIT-T15 cells. 197 39

The present study examines the effect of dopamine (DA), known to inhibit prolactin (PRL) release, on voltage-activated calcium currents in identified rat lactotrophs. Two types of voltage-dependent Ca2+ currents were recorded using the whole-cell mode of the patch-clamp technique. Both were reversibly inhibited by DA application. The inhibitory action of DA was reduced by (i) sulpiride (D2 antagonist), (ii) preincubation of the cells with pertussis toxin (PTX), and (iii) inclusion of guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S) in the pipette solution, whereas it was potentiated by guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S). This DA-induced response could not be overcome by changing the adenosine 3',5'-cyclic monophosphate level. These findings suggest that DA can inhibit Ca2+ entry through voltage-activated Ca2+ channels via a PTX-sensitive G protein(s) pathway thereby affecting PRL release from rat lactotrophs.
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PMID:A guanine nucleotide-binding protein mediates the inhibition of voltage-dependent calcium currents by dopamine in rat lactotrophs. 197 91

Phospholipase C (specific for inositol lipids) is known to be present both in membranes and cytosol. Receptor-mediated activation of this enzyme occurs via a guanine nucleotide regulatory protein (G-protein), designated Gp. We have compared the stimulation of this enzyme by fMet-Leu-Phe via the G-protein in HL60 membranes and in permeabilised cells. fMet-Leu-Phe stimulated phospholipase C in membranes at 2 min and the response was dependent on exogenously added GTP. GTP alone also stimulated phospholipase C activity such that at 10 min the response to fMet-Leu-Phe was minimal. In comparison, the response to fMet-Leu-Phe in permeabilised cells was greater in extent but did not require added GTP. However, it was antagonized by GDP analogues (GDP[beta S] greater than GDP greater than dGDP) and by pertussis toxin pretreatment, indicating that fMet-Leu-Phe-stimulated phospholipase C activity was also mediated via Gp. GTP and its analogue GTP[gamma S] also stimulated phospholipase C and their effects were strictly additive to the stimulation obtained with fMet-Leu-Phe. Such additivity was also observed when two receptor-directed agonists, fMet-Leu-Phe and ATP, were used to stimulate intact cells. It is concluded that (a) the size of the response with fMet-Leu-Phe in membranes is limited by the loss of a component, possibly phospholipase C, and (b) stoichiometry and physical organisation of multiple species of G-proteins and/or phospholipases C may explain the independent nature of phospholipase C activation by fMet-Leu-Phe, ATP and guanine nucleotides.
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PMID:Characterization of fMet-Leu-Phe-stimulated phospholipase C in streptolysin-O-permeabilised cells. 201 14

In membranes of rat striatum, phorbol 12-myristate 13-acetate (PMA), a potent activator of Ca2+/phospholipid-dependent protein kinase, enhanced adenylate cyclase activity by counteracting the inhibition elicited by GTP. Exposure to pertussis toxin caused a similar alteration of the GTP-regulation of the enzyme activity and largely prevented the PMA effects. PMA treatment increased by threefold the GTP requirement of acetylcholine-induced inhibition of adenylate cyclase activity but did not affect the GTP-dependence of the enzyme stimulation by dopamine. The hydrolysis of GTP by membrane-bound high affinity GTPase was significantly inhibited by PMA (IC 50 10 nM) in a Ca2(+)-dependent manner. Like PMA, phorbol 12,13-dibutyrate inhibited the GTPase activity, whereas the biologically inactive 4-beta phorbol 13-acetate and 4-beta phorbol were without effect. These results suggest that activation of Ca2+/phospholipid-dependent protein kinase by PMA stimulates adenylate cyclase activity by impairing the activity of the GTP-dependent inhibitory protein, possibly through a reduction of the GTP-GDP exchange.
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PMID:Alteration of the GTP-dependent inhibitory pathway of rat striatal adenylate cyclase by phorbol esters. 208 70

The regulation of prostacyclin (PGI2) synthesis by cultured human umbilical vein endothelium (HUVEC) was investigated. HUVEC monolayer generation of PGI2 was monitored by RIA of 6-keto PGF1 alpha and dose-dependent increases observed with human alpha- and gamma-thrombins, histamine, or arachidonate. Alpha thrombin (10 nM) produced levels of 6-keto PGF1 alpha approximating responses with 1 microM gamma-thrombin, 5 microM arachidonate, or 10 microM histamine. Diisopropyl phosphorofluoridate-inactivated alpha-thrombin did not stimulate PGI2 release, demonstrating that catalytic activity was required for thrombin-stimulated PGI2 release. Sodium fluoride (NaF), at concentrations known to activate guanine nucleotide regulatory proteins (G proteins), directly stimulated HUVEC PGI2 synthesis in a dose-dependent and time-dependent manner (20 mM NaF, 4.4 +/- 0.5-fold increase at 10 min, 11.9 +/- 1.5-fold increase at 30 min). Neither alpha-thrombin nor NaF-stimulated PGI2 release was dependent upon the availability of extracellular Ca++). The hypothesis that G proteins are involved in agonist-stimulated PGI2 synthesis was further supported by studies using digitonin-permeabilized HUVEC monolayers challenged with another G protein activator, guanosine 5'-0-3-thiotrisphosphate (GTP gamma S), which effected significant dose-dependent increases in PGI2 synthesis compared with control levels of 6-keto PGF1 alpha. In contrast, the G-protein inhibitor GDP beta S, (guanosine 5'-0-2-thiodiphosphate), attenuated alpha-thrombin-mediated prostaglandin generation. Treatment of HUVEC monolayers with pertussis toxin (1 microgram/ml) did not inhibit the PGI2 synthesis stimulated by either alpha-thrombin, NaF, or histamine but catalyzed the ADP ribosylation of a 40 kDa membrane protein which cross-reacted with antisera against a synthetic peptide corresponding to an amino acid sequence common to the alpha-subunit of other G-proteins. Preincubation of HUVEC microsomal membranes with alpha-thrombin diminished pertussis toxin-catalyzed ADP ribosylation in a time-dependent manner. These data suggest that thrombin stimulation of PGI2 synthesis by HUVEC monolayers requires the catalytically functional enzyme and further suggests that the thrombin-occupied receptor is coupled to phospholipase activities by a pertussis toxin-insensitive guanine nucleotide regulatory protein in human endothelial cell membranes.
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PMID:Thrombin-induced prostacyclin biosynthesis in human endothelium: role of guanine nucleotide regulatory proteins in stimulus/coupling responses. 210 25

The native pertussis toxin sensitive GTP-binding proteins (Gi proteins) were individually resolved, and their guanine nucleotide binding and release properties were studied. Gi2 and Gi3, the two major GTP-binding proteins of human erythrocytes, were purified to apparent homogeneity by fast protein liquid chromatography. Gi1 was purified from bovine brain. The three proteins bound 0.6-0.85 mol of guanosine 5'-O-(thio-triphosphate (GTP gamma S)/mol of protein with similar affinities (KD(app) = 50-100 nM). The rate of [35S]GTP gamma S binding to Gi2 was 5-8-fold faster than to Gi1 or Gi3 at 2 mm Mg2+. There were no observable differences in the binding characteristics between bovine brain Gi1 and human erythrocyte Gi3. At 50 mM Mg2+, all three Gi proteins exhibited fast binding, although Gi1 and Gi3 were marginally slower than Gi2. All three Gi proteins exhibited different rates of [32P]GDP release at 2 mM Mg2+. GDP release from Gi2 was severalfold faster than that from Gi1 or Gi3. GDP release rates from Gi1 and Gi3 were similar, although Gi3 was somewhat (60-80%) faster than Gi1. These data indicate that rates of GDP release and GTP binding may be independently regulated for these three proteins and that the relative proportions of Gi2/Gi1 or Gi2/Gi3 will be a crucial factor in determining the kinetics of signal transduction through Gi-coupled effectors.
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PMID:Distinct guanine nucleotide binding and release properties of the three Gi proteins. 210 58

Two distinct light-regulated G-proteins were found in octopus photoreceptors. Gip, a 41 kDa protein from washed microvilli, was ADP ribosylated by pertussis toxin in the presence of GDP in the dark. Light and GTP analogues were inhibitory as with transducin (Gt; G-protein in vertebrate photoreceptors). G34, a 34 kDa protein from fresh octopus retina, was ADP ribosylated by both cholera and pertussis toxin in the dark. Light inhibited labeling of the 34 kDa protein by both toxins. Unlike Gip, G34 is soluble and is very labile to heat, freezing and thawing. Prolonged incubation of octopus retina with cholera toxin and labeled NAD produced an additional radioactive band at 46 kDa. Labeling of the 46 kDa protein, Gsp, was greatly enhanced by GTP analogues, but inhibited by a GDP analogue as with Gs in hormone-sensitive adenylate cyclase. In contrast to Gip and G34, labeling of the 46 kDa protein (Gsp) was not influenced by light. The two distinct light-regulated G-proteins, Gip and G34, found in octopus photoreceptors might be involved in either phototransduction or photoadaptation. The function of Gsp is not known.
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PMID:Two distinct light regulated G-proteins in octopus photoreceptors. 210 29


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