Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have shown previously that stimulation of high-affinity GTP hydrolysis and inhibition of adenylate cyclase activity by muscarinic agonists are mediated by pertussis toxin (IAP) substrates (Gi and Go) in canine cardiac sarcolemma. We have now used the pertussis toxin-treated dog as a whole animal model in which Gi- and Go-mediated biochemical mechanisms can be studied. Mongrel dogs were injected intravenously with IAP 48 hours prior to death and isolation of left ventricular sarcolemma. Treatment of the animal in vivo with the toxin prevented subsequent in vitro IAP-catalyzed [32P]ADP-ribosylation of substrates in cardiac, erythrocytic, and renal cortical plasma membranes, suggesting that ADP-ribosylation occurred in vivo from endogenous substrate. Consistent with our previous results obtained by treating sarcolemma in vitro with IAP, muscarinic receptor-mediated stimulation of high-affinity GTP hydrolysis and inhibition of GTP-activated adenylate cyclase activity were attenuated in sarcolemma purified from the toxin-treated animals. Proximal to adenylate cyclase, guanine nucleotide regulation of muscarinic receptor affinity for agonists was also abolished in membranes from the toxin-treated animals. In addition, the ability of oxotremorine to attenuate GTP regulation of stimulation of adenylate cyclase activity by magnesium ions was abolished in sarcolemma from the IAP-treated dogs. Thus, cardiac sarcolemma isolated from the IAP-treated animals displayed biochemical characteristics of an adenylate cyclase system in which inhibitory regulatory pathways had been attenuated. The cardiac biochemical studies and the in vivo ADP-ribosylation of noncardiac IAP substrates also suggests considerable potential use of this model in the physiological and biochemical study of regulatory mechanisms mediated by GTP-binding proteins in other systems.
 ...
PMID:Pertussis toxin-treated dog: a whole animal model of impaired inhibitory regulation of adenylate cyclase. 335 81

We have investigated whether cholera toxin (CT)- or pertussis toxin (IAP)-sensitive G proteins are involved in ovine (o) PRL-stimulated mitogenesis in the lactogen-dependent rat Nb2 node lymphoma cell line. Addition of IAP to medium caused a biphasic effect on oPRL-stimulated cell number. Low doses (10(-3) ng/ml) enhanced (mean +/- SEM, 15 +/- 3%) whereas higher doses (greater than or equal to 10 ng/ml) inhibited (24 +/- 3%) mitogenesis stimulated by a submaximal dose of oPRL (0.1 ng/ml) compared to control values. The cAMP analog 8-bromo-cAMP also had a biphasic effect on cell division stimulated by submaximal doses of PRL. Low doses (10(-5) M) enhanced whereas higher doses (10(-3) M) inhibited Nb2 cell growth in response to PRL. Incubation with CT only inhibited oPRL-stimulated mitogenesis in a dose-dependent manner. Maximal inhibition (63 +/- 7%) occurred at a concentration of 10 ng/ml or more. Phorbol myristate acetate (PMA) enhanced mitogenesis stimulated by PRL alone and in the presence of either stimulatory or inhibitory doses of IAP, but PMA did not block IAP inhibition. In contrast, PMA had no effect on cells incubated with CT; the inhibition of PRL-stimulated cell division by CT remained unchanged. Lactogenic receptor-binding sites per cell and affinity were not significantly affected by PMA, IAP, or CT, suggesting a postreceptor mechanism of action. In summary, these data demonstrate that cAMP modifies PRL-stimulated Nb2 cell mitogenesis. The differences between IAP and CT (i.e. biphasic effect, degree of inhibition, and differential effect of PMA) suggest that these agents could also modulate PRL actions in the Nb2 cell through different mechanisms, including a cAMP-independent pathway.
 ...
PMID:Modulation of prolactin-stimulated Nb2 lymphoma cell mitogenesis by cholera toxin and pertussis toxin. 338 78

One component of muscarinic receptor inhibition of the function of cardiac ventricles is mediated by the inhibition of activated adenylate cyclase activity in sarcolemma. We have shown previously that muscarinic agonists inhibit GTP- but not Gpp(NH)p-activated adenylate cyclase activity, and various studies in other tissues indicate that nonhydrolyzable GTP analogues prevent inactivation of the enzyme. These data have suggested a role for GTP hydrolysis in the mechanism of inhibition of adenylate cyclase. The present study demonstrates that purified canine cardiac sarcolemma displays high-affinity GTPase activity that is reciprocally related to adenylate cyclase activity. The high-affinity GTPase activity was stimulated by muscarinic agonists and blocked by atropine. Furthermore, the one-half maximal effects of oxotremorine for binding to muscarinic receptors, stimulation of high-affinity GTPase activity, and inhibition of adenylate cyclase activity were similar. Muscarinic stimulation of GTPase activity and inhibition of adenylate cyclase activity required functional activity of the pertussis toxin (IAP) substrate(s). Treatment of sarcolemmal membranes with IAP attenuated the ability of oxotremorine to both stimulate high-affinity GTPase activity and inhibit adenylate cyclase activity. These studies indicate that muscarinic receptor stimulation of high-affinity GTPase activity dependent on functional IAP substrate(s) is closely linked to the mechanism of muscarinic inhibition of adenylate cyclase activity.
 ...
PMID:Muscarinic cholinergic-receptor stimulation of specific GTP hydrolysis related to adenylate cyclase activity in canine cardiac sarcolemma. 339 55

To identify age-related changes in the dopamine (DA) receptors-GTP-binding protein-adenylate cyclase system, the following experiments were performed at 7 days (infant), 70 days (adult) and 2 years (senescent) in striatal membranes of rats: (1) effects of GTP in the presence and absence of pertussis toxin (islet-activating protein, IAP) on adenylate cyclase in the presence of forskolin alone, (2) the same in the presence of forskolin plus DA and (3) the corresponding effect of guanyl-5'-yl-beta, alpha-imido-diphosphate (GppNHp). GTP caused biphasic effects: the activation at 1 microM and the inhibition at 100 microM on forskolin-stimulated cyclase activity at 70 days. The inhibition was suppressed with IAP pretreatment. In infant membranes, 100 microM GTP inhibited the activity in the absence and presence of 100 microM DA and IAP induced a reversal from the inhibition to the stimulation only in the presence of DA. In senescent animals, neither GTP nor IAP affected the activity. GppNHp at 1, 10 and 100 microM only activated and did not inhibit forskolin-stimulated cyclase at each stage. GppNHp-caused stimulation was no more affected by IAP. IAP ADP-ribosylated 41,000 dalton proteins at each stage and the specific activity of ADP-ribosylation was not changed during development and aging. It is suggested that inhibitory GTP-binding protein (Gi) with molecular size of 41,000 dalton is involved in DA receptor-adenylate cyclase system whose function is low at infant stage and markedly decreased at senescent stage in rat striatal membranes.
 ...
PMID:Influences of pertussis toxin, guanine nucleotides and forskolin on adenylate cyclase in striatal membranes of infant, adult and senescent rats. 350 4

We compared the effects of guanine nucleotides and Mg2+ on ADP-ribosylation of rat brain and liver membrane proteins catalysed by Bordetella pertussis toxin (IAP) and cholera toxin (CT). Labelling of proteins in the presence of [alpha-32P]NAD+, ATP and CT required GTP or guanosine 5'-[gamma-thio]triphosphate (GTP [S]). In contrast, labelling of one (liver) or two (brain) polypeptides by IAP was enhanced by guanosine 5'-[beta-thio]diphosphate (GDP[S]) or GTP, but was blocked by GTP[S] or guanosine 5'-[beta, gamma-imido]triphosphate (p[NH]ppG). The order of labelling intensity was GDP[S] greater than GTP greater than no addition greater than GTP[S] = p [NH]ppG. Mg2+ increased labelling by CT, but decreased labelling by IAP. In addition, Mg2+ potentiated the effects of the guanine nucleotides, increasing the inhibitory effects of GTP[S] and the activatory effects of GDP[S] or GTP. Preincubating liver membranes at 30 degrees C in the presence of 10 mm-MgCl2 inhibited labelling by IAP irreversibly. Pretreatment of liver membranes with 4.95 mM-N-ethylmaleimide decreased labelling by CT by approximately 15%, but almost completely blocked labelling by IAP. These results suggest that the undissociated, GDP-bound, conformation of Ni, the inhibitory GTP-binding protein of adenylate cyclase, is the preferred substrate for ADP-ribosylation by IAP. This conformation, which is prevalent in native membranes, is sensitive to temperature, Mg2+ ions and alkylating agents such as N-ethylmaleimide. At 30 degrees C, Mg2+ may cause dissociation and denaturation of Ni in native membranes.
 ...
PMID:Pertussis toxin substrate is a guanosine 5'-[beta-thio]diphosphate-, N-ethylmaleimide-, Mg2+- and temperature-sensitive GTP-binding protein. 393 83

Cyclic adenosine 3',5'-monophosphate (cAMP) plays a critical role in modulating a variety of neuronal responses in Aplysia californica. Previous studies have focused on the neurotransmitter activation of adenylate cyclase, which presumably occurs via the guanosine 5'-triphosphate (GTP)-regulated excitatory subunit (Ns). While adenylate cyclase has also been shown to be regulated by inhibitory neurotransmitters, coupled through the inhibitory GTP-regulated coupling protein Ni in some systems, the effects of Ni-mediated adenylate cyclase inhibition on neuronal processing in Aplysia have not previously been reported. In the present study Ni is detected in Aplysia by both protein chemistry and enzymatic activity. A 40 kdalton substrate for the enzymatic activity of Bordetella pertussis toxin is observed. Incubation of Aplysia nervous tissue homogenates with pertussis toxin (IAP) and 32P-nicotinamide-adenine dinucleotide labels a single protein, assessed by polyacrylamide gel electrophoresis and autoradiography. Furthermore, crude membrane suspensions of this tissue demonstrate biphasic adenylate cyclase activity in response to increasing concentrations of GTP, showing Ni and Ns functional activities. These findings provide evidence that Ni is present in Aplysia tissue. Ni may serve as an important site for the regulation of cAMP synthesis and neuronal plasticity.
 ...
PMID:Evidence for the inhibitory subunit of adenylate cyclase (Ni) in nervous and heart tissue of Aplysia. 396 Mar 97

The longitudinal muscle-myenteric plexus preparation of the guinea-pig ileum has been employed for the study of the effect of pertussis toxin (IAP) on opioid dependence. Guinea-pigs were treated with IAP (120 micrograms/kg, i.p.) either prior to chronic administration of an opioid or after opioid dependence had been established. The isolated preparations were tested in vitro for dependence; that is, the naloxone-precipitated withdrawal contracture. Naloxone almost failed to evoke a sign of dependence in preparations treated with IAP prior to chronic exposure to an opioid. In contrast, IAP failed to affect the withdrawal contracture when applied to an animal after dependence has been established. It is concluded that the Ni-unit, the substrate for IAP, plays a critical function in the development of dependence. The continuous activation of the opioid receptor associated with the development of dependence may induce changes in Ni which in turn prevent the interaction of IAP with its substrate.
 ...
PMID:Opioid dependence prevents the action of pertussis toxin in the guinea-pig myenteric plexus. 405 98

Treatment of guinea pig neutrophils with pertussis toxin (islet-activating protein; IAP) results in inhibition of N-formyl peptide receptor-mediated release of arachidonic acid and granular enzymes. Inhibition by the toxin is specific, in that responses to the calcium ionophore A23187 are not affected. The action of the toxin is not associated with alterations in cellular concentrations of cyclic AMP but is correlated with the ability of the toxin to catalyze the ADP-ribosylation of a 41,000 dalton membrane protein. This protein comigrates on SDS-polyacrylamide gels with the alpha subunit of Gi, the inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase. It is likely that this G protein is involved in receptor-mediated signal transduction in neutrophils by mechanisms that do not involve cyclic AMP.
 ...
PMID:Inhibition of receptor-mediated release of arachidonic acid by pertussis toxin. 609 10

Both calcitonin and prostaglandin E2 (PGE2) stimulate adenylate cyclase activity in the human breast cancer cell line (T 47D). The maximum cyclic AMP response to calcitonin exceeds that of PGE2. When maximal concentrations of the two hormones were added simultaneously to the cells, the amount of cyclic AMP generated was less than that seen with calcitonin alone. When cells were treated with the protein toxin of Bordetella pertussis (islet-activating protein; IAP) which inactivates the inhibitory regulatory component (Ni) of adenylate cyclase, there was no change in basal or calcitonin-responsive adenylate cyclase in intact cells. However, the PGE2 response was augmented at all dose levels, and this effect was dependent on the concentration of IAP. Moreover, in cells pretreated with IAP, simultaneous addition of PGE2 and calcitonin resulted in additivity rather than in inhibition of cyclic AMP production. The additivity of the response to calcitonin and PGE2 after IAP treatment implies activation of separate pools of adenylate cyclase catalytic subunit by the two hormones. These data are consistent with a model in which calcitonin acts on adenylate cyclase in T 47D cells through stimulatory regulatory components alone, whereas PGE2 acts on the same cells through both stimulatory and inhibitory components. The Ni input can limit the maximum effect of PGE2 and is capable of limiting calcitonin effects when the two agonists are used simultaneously.
 ...
PMID:Effects of pertussis toxin on adenylate cyclase responses to prostaglandin E2 and calcitonin in human breast cancer cells. 609 15

Islet-Activating Protein, purified from the culture medium of Bordetella pertussis, enhanced glucose-induced insulin secretion from cultured neonatal rat islets in a calcium dependent manner. This effect was accompanied by an increase in lipid associated Ca2+ ionophoretic activity, as measured by passage of Ca2+ through multilamellar planar membranes containing islet lipid extracts. These findings suggest that the action of IAP in the neonatal islet may be mediated by enhanced entry of extracellular calcium following an effect on membrane lipid composition.
 ...
PMID:Enhanced glucose-induced insulin release and endogenous Ca2+ ionophoretic activity in neonatal rat islets following islet-activating protein. 634 18


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>