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)

The binding of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine to its cell surface receptor rapidly elicits the hydrolysis of phosphatidylinositol 4,5-bisphosphate by phospholipase C to form the putative second messengers inositol 1,4,5-trisphosphate and sn-1,2-diacylglycerol. To investigate the possible role of a guanine nucleotide binding protein in transduction of this membrane signal, we examined the effects of pertussis toxin on chemotactic peptide-stimulated inositol phospholipid metabolism in differentiated HL-60 cells labeled with [3H]inositol. Pertussis toxin inhibited the chemotactic tripeptide-stimulated production of inositol mono-, bis-, and trisphosphates and secretion of N-acetyl-beta-D-glucosaminidase in a time- and concentration-dependent manner. Treatment with pertussis toxin did not alter the total incorporation or the distribution of [3H]inositol in inositol phospholipid. Chemotactic peptide receptor number was unchanged, although a slight decrease in binding affinity was observed. These findings suggest a role for a guanine nucleotide binding protein in coupling the chemotactic peptide receptor to phospholipase C.
 ...
PMID:Pertussis toxin inhibits chemotactic peptide-stimulated generation of inositol phosphates and lysosomal enzyme secretion in human leukemic (HL-60) cells. 286 Jun 68

Both forskolin, the activator of adenylate cyclase, and 8-bromocyclic (cAMP) increase cytosolic calcium levels (measured using Quin 2) and adrenocorticotropin (ACTH) release from a tumor cell line of the mouse anterior pituitary (AtT-20/D16-16). Somatostatin (SRIF) blocks the ACTH release response to each secretagogue but only inhibits forskolin-stimulated calcium mobilization suggesting that SRIF prevents the formation of cAMP rather than blocking the ability of cAMP to raise intracellular calcium concentrations. SRIF itself lowers intracellular calcium levels. The ACTH release response but not the rise in cytosolic calcium levels induced by the membrane-depolarizing agent K+, is blocked by SRIF, indicating that SRIF can interfere with some intracellular event, other than calcium mobilization or cAMP formation, to reduce ACTH secretion. Pertussis toxin uncouples SRIF receptors from adenylate cyclase by catalyzing the ADP-ribosylation of an inhibitory guanine nucleotide binding protein (Ni) in AtT-20 cell membranes. Pretreatment of AtT-20 cells with pertussis toxin abolishes the inhibition by SRIF of the ACTH release response and of the rise in cytosolic calcium induced by forskolin. In addition, the ability of SRIF to inhibit basal calcium levels is prevented by pertussis toxin treatment. Pertussis toxin treatment also reduced the ability of SRIF to inhibit K+-evoked ACTH release. SRIF receptor binding studies using the ligand 125I-CGP-23996 revealed that pertussis toxin treatment greatly diminished the affinity of the SRIF receptor for SRIF and its structural analogs. These results indicate that, in addition to coupling SRIF receptors to adenylate cyclase, Ni is also involved in the lowering by SRIF of resting calcium levels.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Pertussis toxin blocks somatostatin inhibition of calcium mobilization and reduces the affinity of somatostatin receptors for agonists. 286 3

The effects of selective alpha adrenoceptor agonists and antagonists on vasopressin (VP)-sensitive cyclic AMP (cAMP) formation in microdissected rat papillary collecting ducts were examined. In the presence of 10(-10) M VP, norepinephrine and the selective alpha-2 adrenoceptor agonist, B-HT 933, produced almost total inhibition of VP-stimulated cAMP accumulation. Half-maximal inhibition occurred at 1 x 10(-8) M and 6 x 10(-7) M for norepinephrine and B-HT 933, respectively. Cirazoline, a selective alpha-1 adrenoceptor agonist, had no significant effect on VP-stimulated cAMP accumulation. The inhibitory effects of norepinephrine and B-HT 933 were antagonized by rauwolscine but not by prazosin. The antagonism of B-HT 933-induced inhibition of VP-stimulated cAMP accumulation was competitive with an antagonist dissociation constant (KB) of 10.9 x 10(-9) M. Preincubation of papillary collecting ducts with pertussis toxin (1 microgram/ml for 1 hr at 37 degrees C) attenuated, by 65%, the inhibitory effect of B-HT 933 on VP-stimulated cAMP levels. These results demonstrate that alpha-2 adrenoceptors capable of inhibiting VP action are present on the papillary collecting duct. Furthermore, the alpha-2 adrenoceptor-induced inhibition of VP-stimulated cAMP accumulation is pertussis-toxin sensitive. This suggests that alpha-2 adrenoceptors are coupled negatively to adenylate cyclase, via the guanine nucleotide binding protein, in the collecting tubule.
 ...
PMID:Inhibition of vasopressin-stimulated cyclic AMP accumulation by alpha-2 adrenoceptor agonists in isolated papillary collecting ducts. 289 53

Injections of N6-(phenylisopropyl)adenosine, a nonmetabolizable adenosine A1 receptor agonist, desensitized rat adipocytes to the drug in 20 h. Lipolysis stimulated by 2 mumol/l DL-isoproterenol was inhibited markedly less by N6-(phenylisopropyl)adenosine in adipocytes isolated from treated than control animals (P less than 0.01). Glucose uptake was more responsive to N6-(phenylisopropyl)adenosine in adipocytes from control than treated animals (P less than 0.02). Adenosine content was the same in adipose tissue of control and treated animals. The number of adenosine binding sites was not significantly lower in treated compared with control animals (1580 +/- 279 and 1988 +/- 575 fmol/mg protein; mean +/- SEM). There was no change in receptor affinity (Kd = 10 nmol/l in both groups). There was no decrease in the amounts of the inhibitory guanine nucleotide binding protein (Gi) alpha subunits as studied by pertussis toxin catalyzed ADP-ribosylation. It is concluded that desensitization to N6-(phenylisopropyl)adenosine can be observed without changes in the adenosine receptor status or decrease in the amount of inhibitory guanine nucleotide binding protein and that adipose tissue adenosine content is not changed by the agonist treatment.
 ...
PMID:Rat adipose tissue adenosine sensitivity and adenosine content after subcutaneous administration of N6-(phenylisopropyl)adenosine. 292 38

Pertussis toxin suppressed [32P]polyphosphoinositide breakdown and lysosomal enzyme secretion induced by fMet-Leu-Phe in rabbit neutrophils. Likewise, fMet-Leu-Phe- or leukotriene B4-evoked [3H]inositol trisphosphate accumulation was inhibited by the toxin. These findings, taken together with evidence that pertussis toxin specifically causes inactivation of the guanine nucleotide binding protein (Ni), suggests that guanine nucleotide binding proteins may mediate coupling between calcium-mobilising receptors and phospholipase C-mediated reactions in rabbit neutrophils.
 ...
PMID:Pertussis toxin inhibits chemotactic factor-induced phospholipase C stimulation and lysosomal enzyme secretion in rabbit neutrophils. 298 32

We have examined several features of the regulation of cyclic AMP accumulation in lymphoid cells isolated from peripheral blood of human subjects and in the murine T-lymphoma cell line, S49, S49 cells are unique because of the availability of variant clones with lesions in the pathway of cyclic AMP generation and response. We found that human lymphoid cells prepared at 4 degrees C showed substantially greater cyclic AMP accumulation in response to histamine and the beta-adrenergic agonist isoproterenol than did cells prepared at ambient temperature. The muscarinic cholinergic agonist carbamylcholine and peptide hormone somatostatin failed to inhibit cyclic AMP accumulation in human lymphoid cells and treatment with pertussis toxin (which blocks function of Gi, the guanine nucleotide binding protein that mediates inhibition of adenylate cyclase) only minimally increased cyclic AMP levels in these cells. Thus the Gi component of adenylate cyclase appears to play only a small role in modulating cyclic AMP levels in this mixed population of lymphoid cells. Incubation of whole blood with isoproterenol desensitized human lymphocytes to subsequent stimulation with beta agonist. This desensitization was associated with a redistribution of beta-adrenergic receptors such that a substantial portion of the receptors in intact cells could no longer bind a hydrophilic antagonist. Wild-type S49 lymphoma cells showed a similar redistribution of beta-adrenergic receptors after a few minutes' incubation with agonist. Based on studies in S49 variants, this redistribution is independent of components distal to receptors in the adenylate cyclase/cyclic AMP pathway. By contrast, a more slowly developing, agonist-mediated down-regulation of beta-adrenergic receptors was blunted in variants with defective interaction between receptors and Gs, the guanine nucleotide binding protein that mediates stimulation of adenylate cyclase. Unlike results in human lymphoid cells, S49 cells show a prominent inhibition of cyclic AMP accumulation mediated by Gi; this inhibition is promoted by somatostatin and blocked by pertussis toxin. Inhibition by Gi is unable to account for the marked decrease in ability of the diterpene forskolin to maximally stimulate adenylate cyclase in S49 variants having defective Gs. These results emphasize that both Gs and Gi component are important in modulating cyclic AMP accumulation and receptors linked to adenylate cyclase in S49 lymphoma cells.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Regulation of cyclic AMP accumulation in lymphoid cells. 299 40

Platelet activating factor has been found to increase the intracellular level of free calcium (as monitored by the fluorescent calcium indicator quin-2) and to stimulate the turnover of the polyphosphoinositides in rabbit neutrophils. Calcium mobilization induced by platelet activating factor, in contrast to previous reports with chemotactic factors, is unaffected by pertussis toxin; on the other hand, stimulated polyphosphoinositol hydrolysis and granule enzyme secretion are potently antagonized under the same conditions. The calcium, as well as the secretory responses to the lipid mediator are largely dependent on the presence of extracellular calcium. Internal contributions to the quin-2 signal are only detectable at relatively high concentrations of platelet activating factor. Calcium mobilization and secretion stimulated by platelet activating factor are inhibited following a short incubation with phorbol 12-myristate 13-acetate. These results are discussed in terms of the possibility that platelet activating factor activates neutrophils via dual pathways, the first involving direct interaction with phorbol ester inhibitable calcium channels and the other the stimulation in a manner dependent on a guanine nucleotide binding protein of the phospholipase C specific for polyphosphoinositides.
 ...
PMID:Unique inhibitory profile of platelet activating factor induced calcium mobilization, polyphosphoinositide turnover and granule enzyme secretion in rabbit neutrophils towards pertussis toxin and phorbol ester. 299 80

Neutrophil responsiveness is initiated by increases in the intracellular concentration of calcium through mechanisms the elucidation of which is of interest to the field of signal transduction in calcium mobilizing systems. Some, but not all, neutrophil chemotactic factors specifically stimulate the hydrolysis of phosphatidylinositol 4,5-bisphosphate. A non-mitochondrial pool of internal calcium has been shown to be released in permeabilized cells by inositol 1,4,5-trisphosphate. Diglyceride is thought to activate protein kinase C producing stimulatory and inhibitory signals for neutrophil activation. The lack of effect of leukotriene B4, on polyphosphoinositide hydrolysis indicates that mechanisms independent of inositol 1,4,5-trisphosphate are also available to the neutrophils. Pertussis toxin inhibits the stimulated mobilization of calcium, hydrolysis of the polyphosphoinositides and activation of protein kinase C. The inhibitory effects of pertussis toxin can be bypassed by phorbol esters and calcium ionophores thus indicating that a guanine nucleotide binding protein is functionally located at a step preceding the activation of phospholipase C. The similarities between the biochemical events activated by chemotactic factors and those described in other hormonally sensitive cells emphasize the generality of the relevance of these concepts. The differences raise the possibility that elements of the excitation-response coupling sequence other than those commonly monitored will still be identified. The later may be more evident in the neutrophils because these cells' predominant function is motility and not secretion.
 ...
PMID:Calcium mobilization and signal transduction in the neutrophils. 299 5

Fluoride ion, at concentrations above 10 mM, was found to elicit a rise in intracellular calcium levels in neutrophils, as monitored by changes in Quin 2 fluorescence intensity. The calcium mobilization response was characterized by a lag period of 4 to 10 min. and a prolonged duration of action (greater than 20 min.). In contrast, the chemotactic peptide, formylmethionyl-leucyl-phenylalanine, induced a rise in intracellular calcium concentrations which peaked within 1 min. Preincubation of the cells with 1 microgram/ml pertussis toxin resulted in inhibition of the formylmethionyl-leucyl-phenylalanine induced response, but not that mediated by fluoride. Recent evidence suggests that the formylmethionyl-leucyl-phenylalanine receptor is coupled to phospholipase C and phosphoinositide degradation through a guanine nucleotide binding protein susceptible to inhibition by pertussis toxin. Present results suggest that fluoride ion may serve to activate this protein in a manner resistant to inhibition by pertussis toxin.
 ...
PMID:Calcium mobilization in fluoride activated human neutrophils. 300 Mar 73

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).
 ...
PMID:Guanine nucleotide binding protein involved in muscarinic responses in the pig coronary artery is insensitive to islet-activating protein. 303 Feb 65


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