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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incubation of particulate fractions of swine granulosa cells or luteal minces with purified pertussis toxin (islet-activating protein) and [32P]-NAD catalyzed the (32P)-ADP ribosylation of a 41,000 dalton membrane protein. ADP-ribosylation was markedly reduced by prior incubation of intact cells with toxin. The functional relevance of this presumptive inhibitory guanine nucleotide-binding protein in pig granulosa cells was indicated by the ability of prior treatment with pertussis toxin to increase cyclic AMP generation and progesterone production significantly in response to follicle stimulating hormone. Prior cellular intoxication also enhanced cyclic AMP production stimulated by luteinizing hormone and choleratoxin, but not basally or after forskolin. These results demonstrate the presence of an inhibitory guanine nucleotide-binding protein in both the follicular (granulosa cell) and luteal compartments of the mammalian ovary, and indicate its functional relevance in cyclic AMP generation and progesterone secretion.
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PMID:Evidence for a functionally active inhibitory guanine nucleotide-binding regulatory protein in the swine ovary. 299 39

Angiotensin II can inhibit glucagon-stimulated cyclic AMP production in hepatocytes and adenylate cyclase activity in hepatic membranes. Pertussis toxin, an exotoxin produced by Bordetella pertussis, was used to investigate the role of the inhibitory guanine nucleotide-binding regulatory protein of adenylate cyclase (Ni) in coupling angiotensin receptors to the adenylate cyclase system. An assay was developed using [32P] NAD+ to quantitate the amount of Ni protein in the membrane and the extent of its ADP-ribosylation catalyzed by toxin. The ability of angiotensin to inhibit adenylate cyclase and interact with its receptor was compared with the degree of modification of Ni in membranes prepared from isolated hepatocytes. In control membranes angiotensin II inhibited basal adenylate cyclase by 35%. When all of the Ni molecules in the membrane were ADP-ribosylated, angiotensin did not inhibit adenylate cyclase. However, the attenuation of angiotensin's effect on cyclase was not linearly correlated with the degree of modification of Ni; ADP-ribosylation of greater than 80% of the Ni was required before a reduction of the angiotensin effect was observed. A possible explanation for this finding is an excess of Ni molecules in the membrane (approximately 3.4 pmol/mg of membrane protein) over angiotensin II receptors (approximately 1.2 pmol/mg of membrane protein). 125I-angiotensin bound to sites in the membrane with two affinities. Computer fitting of the binding isotherms yielded parameters of N1 = 279 fmol/mg protein, Kd1 = 0.2 nM; N2 = 904 fmol/mg protein, Kd2 = 1.4 nM. When all of the Ni molecules in the membrane were ADP-ribosylated, angiotensin bound to only one site with binding parameters of N = 349 fmol/mg protein, Kd = 0.4 nM. GTP-gamma-S caused a 7-fold increase in the Kd of this site to 2.7 nM. Overall, the data indicate that the Ni protein mediates the effect of angiotensin on adenylate cyclase. The observation that GTP-gamma-S can markedly decrease the affinity of angiotensin receptors when all Ni molecules are ADP-ribosylated suggests that angiotensin receptors may couple to other GTP-binding proteins which may mediate the effects of angiotensin in other signal transduction systems.
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PMID:Role of Ni in coupling angiotensin receptors to inhibition of adenylate cyclase in hepatocytes. 299 49

Rabbits immunized with ADP-ribose chemically conjugated to carrier proteins developed antibodies reactive against guanine nucleotide binding proteins (G proteins) that had been mono-ADP-ribosylated by bacterial toxins. Antibody reactivity on immunoblots was strictly dependent on incubation of substrate proteins with both toxin and NAD and was quantitatively related to the extent of ADP-ribosylation. Gi, Go, and transducin (ADP-ribosylated by pertussis toxin) and elongation factor II (EF-II) (ADP-ribosylated by pseudomonas exotoxin) all reacted with ADP-ribose antibodies. ADP-ribose antibodies detected the ADP-ribosylation of an approximately 40-kilodalton (kDa) membrane protein related to Gi in intact human neutrophils incubated with pertussis toxin and the ADP-ribosylation of an approximately 90-kDa cytosolic protein, presumably EF-II, in intact HUT-102 cells incubated with pseudomonas exotoxin. ADP-ribose antibodies represent a novel tool for the identification and study of G proteins and other substrates for bacterial toxin ADP-ribosylation.
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PMID:Immunochemical detection of guanine nucleotide binding proteins mono-ADP-ribosylated by bacterial toxins. 302 18

Neuropeptide Y, a major neuropeptide and potent vasoconstrictor, inhibited isoproterenol-stimulated adenylate cyclase activity in cultured rat atrial cells as well as in atrial membranes. Prior treatment of the cells with pertussis toxin blocked the inhibitory action of neuropeptide Y. Pertussis toxin is known to uncouple the receptors for other inhibitors of adenylate cyclase by ADP-ribosylation of the alpha-subunit of Gi, the inhibitory guanine nucleotide binding component of adenylate cyclase. The toxin specifically catalyzed the ADP-ribosylation of a 41-kilodalton atrial membrane protein which corresponded to the Gi subunit. These results suggest that neuropeptide Y may mediate some of its physiological effects through specific receptors linked to the inhibitory pathway of adenylate cyclase.
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PMID:Neuropeptide Y inhibits cardiac adenylate cyclase through a pertussis toxin-sensitive G protein. 302 13

In an attempt to identify the nature of guanine nucleotide binding protein(s) (G-protein) involved in the acetylcholine (ACh)-induced (muscarinic) response of pig coronary-artery smooth muscle, we studied the effect of ADP-ribosylation of specific membrane protein(s) catalysed by islet-activating protein (IAP; pertussis toxin). The ACh-stimulated and guanine nucleotide-dependent activities of phosphatidylinositol 4,5-bisphosphate (PIP2) phosphodiesterase (PDE), assessed by the production of inositol 1,4,5-trisphosphate (IP3) from exogenously applied PIP2, were not modified, in either IAP-treated or non-treated cell homogenates used as the enzyme source. In intact tissues, pretreatment with up to 100 ng of IAP/ml inhibited neither the ACh-induced decrease in the amount of inositol phospholipids nor the increase in the amounts of phosphatidic acid and of inositol phosphates. IAP treatment increased the amount of cyclic AMP accumulated by isoprenaline. These observations suggest that G-protein which couples the muscarinic receptor to PIP2-PDE is insensitive to IAP. Such being the case, the nature of this protein(s) probably differs from that required for the regulation of adenylate cyclase activities (Ni or Gi).
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PMID:Guanine nucleotide binding protein involved in muscarinic responses in the pig coronary artery is insensitive to islet-activating protein. 303 Feb 65

Amounts of the guanine nucleotide binding regulatory proteins which are also pertussis toxin substrates (such as Ni and No) were measured in rat glioma, C6BU-1, cells and in neuroblastoma X glioma, NG108-15, hybrid cells. Measurements were performed both by quantitating pertussis toxin catalyzed ADP-ribosylation and by quantitative immunoblotting with affinity purified antibodies specific for Ni or No. The amounts of pertussis toxin substrate in C6 and NG108-15 cells are 7.5 and 0.6 pmol/mg membrane protein, respectively. These levels are minimum values and higher estimates of the total amounts of N proteins in the two cells are obtained by quantitative immunoblot analysis of the beta-subunit common to all N proteins. Immunoblots with specific antibodies show that NG108-15 cells contain 3.8 pmol/mg of No and detectable but small (less than 0.1 pmol/mg) amounts of Ni. In contrast, C6 cell membranes contain no detectable No and only 0.14 pmol/mg Ni. Thus, C6 cells contain large amounts of a pertussis toxin substrate which is neither Ni nor No.
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PMID:The GTP-binding regulatory proteins of neuroblastoma x glioma, NG108-15, and glioma, C6, cells. Immunochemical evidence of a pertussis toxin substrate that is neither Ni nor No. 308 Mar 32

Pertussis toxin (islet-activating protein) treatment of intact Swiss 3T3 cells causes a time- and dose-dependent loss of availability of a 40 kDa membrane protein for toxin-catalyzed ADP-ribosylation in subsequent incubations with [32P]NAD. In parallel, [3H]thymidine uptake by quiescent cells stimulated with fresh serum, cell doubling time and cell saturation density are all decreased 30-50%. These results cannot be accounted for by the potential effect of the toxin on cell cAMP levels. They suggest that a pertussis toxin substrate, probably Gi, modulates some component of growth regulation in Swiss 3T3 cells.
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PMID:Pertussis toxin alters the growth characteristics of Swiss 3T3 cells. 308 83

It has been reported recently (Begin-Heick, N. (1985) J. Biol. Chem. 260, 6187-6193) that adipocytes from the obese mouse strain (ob/ob), unlike normal mice (+/+), lack functional Gi, a GTP-regulated protein complex that mediates inhibition of adenylate cyclase. In contrast, we have found functional Gi linked to inhibition of adenylate cyclase in adipocyte membranes from both ob/ob and +/+ mice. This conclusion is based on observation of: 1) GTP-dependent inhibition of adenylate cyclase by antilipolytic agents, such as prostaglandin E2, nicotinic acid, and the adenosine receptor agonist, phenylisopropyladenosine (PIA); 2) classical biphasic GTP kinetics, with stimulation by low and inhibition by high concentrations of GTP; and 3) elimination of cyclase inhibition by antilipolytic agents upon treatment of ob/ob adipocytes with pertussis toxin. Upon treatment with pertussis toxin and [32P] NAD, purified adipocyte membranes from ob/ob mice incorporated twice as much radioactivity per unit membrane protein than those from +/+ mice in the 40,000-42,000 region. The inhibitory actions of PIA on adenylate cyclase were blocked by the adenosine receptor antagonists, theophylline and isobutylmethylxanthine. However, in contrast to other known inhibitory adenosine receptors, relatively high (100 nM) PIA concentrations were required for half-maximal inhibition of adenylate cyclases from both +/+ and ob/ob adipocytes. The adipocyte adenylate cyclase from both mouse strains were approximately equally susceptible to inhibition by nicotinic acid and prostaglandin E2. However, the ob/ob cyclase was inhibited by 47% with PIA, whereas the enzyme from the +/+ mouse was inhibited by only 27% (p less than 0.01). This greater inhibition by adenosine may contribute to abnormal fat metabolism in adipocytes from ob/ob mice.
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PMID:Presence of a functional inhibitory GTP-binding regulatory component, Gi, linked to adenylate cyclase in adipocytes of ob/ob mice. 310 20

The complexion of the adenylate cyclase system and in particular, the regulation of G-proteins was examined in 3T3-L1 cells during differentiation from a fibroblast-like to an adipocyte-like phenotype. Gs alpha (the identified regulatory component of hormone-sensitive adenylate cyclase that mediates stimulation), measured by cholera toxin-catalyzed ADP-ribosylation, increased by approximately 6-fold from day 0 to day 8. Gs alpha, measured by functional reconstitution, increased in specific activity by approximately 3-fold from day 0 to day 8. Both Gi alpha (the G-protein with alpha-subunit Mr 40,000-41,000 whose function is in part the mediation of inhibition of adenylate cyclase) and Go alpha (the highly abundant G-protein first isolated from bovine brain whose effector system remains to be established) measured by pertussis toxin-catalyzed ADP-ribosylation increased by approximately 4-fold over this same period. 3T3-L1 cells possess beta-subunits of G-proteins displaying Mr = 36,000 (beta 36) and Mr = 35,000 (beta 35). The increase in the beta 35 as well as beta 36 subunits was approximately 2-fold. Using quantitative immunoblotting techniques and specific antisera, the total amount of beta-subunits was determined to be 150 as compared to 70 pmol/mg of membrane protein, while the amount of Go alpha was 40 and 10 pmol/mg of membrane protein in adipocytes and fibroblasts, respectively. Since Go alpha is the most abundant G-protein alpha-subunit observed to date in both phenotypes, the overall ratio of beta- to alpha-subunits of G-proteins appears to decrease from approximately 4.7 in fibroblasts to 2.5 in adipocytes. These data suggest that in differentiation not only is the complexion of G-proteins altered but more importantly, the relative amounts of alpha- to beta-subunits are regulated.
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PMID:Regulation of G-proteins in differentiation. Altered ratio of alpha- to beta-subunits in 3T3-L1 cells. 311 49

Membrane fractions prepared from rat striate, cortex and midbrain were treated with pertussis toxin, which has been shown to adenosine diphosphate (ADP)-ribosylate the GTP-binding protein Gi, reducing its coupling with receptors. In striatal membranes, treatment with 40 micrograms toxin per mg membrane protein labeled 60% of the Gi present and 70% of another G protein, Go; this treatments reduced binding of the opioid agonist [3H]D-Ala2-D-Leu5-enkephalin ([3H]DADLE) 20-50%, with the decrease largely reflecting a decreased affinity. In cortex, toxin treatment reduced [3H]DADLE binding by 35-70%, corresponding to ADP-ribosylation of 50% of Gi and 40% of Go. In midbrain, [3H]DADLE binding was unaffected by toxin treatment that ADP-ribosylated 86% of the Gi and 72% of the Go. These results provide further evidence that opioid receptors are associated with GTP-binding proteins in striatum and cortex, where they have also been shown to inhibit adenylate cyclase. Despite the presence of Gi and Go in midbrain, however, there appears to be no coupling between them and opioid receptors.
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PMID:Modification of opioid agonist binding by pertussis toxin. 311 72


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