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)

Collagen fibres in suspension have been shown to inhibit adenylate cyclase in human platelet preparations. Direct inhibition by collagen fibres was observed when intact platelets were used, although secondary events such as ADP secretion or prostanoid formation were important contributors to the inhibition of adenylate cyclase after treatment of platelets with collagen. The nature of the direct inhibition caused by collagen has been investigated in platelet membrane preparations, with the following results. (1) Collagen fibres inhibit platelet membrane adenylate cyclase in a dose-dependent manner. (2) Inhibition of adenylate cyclase by thrombin, adrenaline or collagen fibres could be abolished in the presence of guanosine 5'-[beta-thio]diphosphate; half-maximal inhibition was obtained at about 100 microM for the inhibitory action of thrombin, and at about 500 microM for that of either adrenaline or collagen. (3) The action of each ligand was blocked to a similar extent by pertussis-toxin treatment of the platelet membranes. Taken together, these results indicate that the action of collagen, like that of thrombin and adrenaline, is G-protein-dependent. (4) inhibition of adenylate cyclase by collagen fibres was additive with that caused by adrenaline, but co-operative with that caused by thrombin, suggesting that inhibitory pathways exists for collagen and adrenaline which are distinct from, but interactive with, that for thrombin. (5) Modification of the collagen fibres by pepsin treatment attenuated the effects of collagen, whereas heat-denaturation of the collagen fibres completely abolished their effects. These data suggest that the effects of collagen are specific, and depend on the detailed structure of the collagen fibres.
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PMID:Inhibition of human platelet adenylate cyclase by collagen fibres. Effect of collagen is additive with that of adrenaline, but interactive with that of thrombin. 131 55

C1q, a plasma glycoprotein and the recognition component of the classical complement pathway, interacts with specific cells of the immune system resulting in the enhancement of cell function. For example, interaction of C1q with its cell-surface receptor on neutrophils induces the activation of the respiratory burst, a finding previously documented using a chemiluminescent assay to detect oxygen radical formation. In an alternative approach we have now used a modified cytochrome c reduction assay to characterize C1q-mediated production of superoxide anion (O2-) in more detail. C1q coated to microtiter wells induced O2- release, which occurred microtiter wells induced O2- release, which occurred after a lag period of 10 to 20 min, and was then sustained over approximately 1 h. O2- production could be triggered by the purified pepsin-resistant, collagen-like fragment of C1q, but not by mannose-binding protein and pulmonary surfactant protein A, proteins that also contain collagen-like domains. Concentrations of C1q which promoted a vigorous O2- generation did not induce release of neutrophil primary granules and caused little or no secondary granule release. Investigation of the biochemical events mediating C1q stimulated O2- production by neutrophils revealed that the response invoked two biochemical pathways with distinct sensitivities to previously described inhibitors. A role for Ca2+ in initiation of the response was suggested by the inhibitory effect of EGTA, the calmodulin antagonist W7, and the intracellular Ca2+ chelator BAPTA. The protein kinase inhibitor staurosporine did not inhibit the induction of the response, but did block that component of the response occurring after approximately 30 min. Neither phase of C1q-mediated O2- production was inhibited by pertussis toxin, a strong inhibitor of the G-protein-coupled FMLP-mediated response. In summary, C1q-triggered O2- production is relatively unique both in terms of the kinetics of the response and the biochemical pathways evoked. These data support the hypothesis that more than one biochemical pathway induced by ligand-receptor interaction can activate the neutrophil NADPH oxidase.
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PMID:Signal transduction mechanisms of C1q-mediated superoxide production. Evidence for the involvement of temporally distinct staurosporine-insensitive and sensitive pathways. 131 35

Acid secretory activity and respiration in rabbit gastric glands are stimulated by cAMP-dependent and -independent agonists. Potentiation between agonists suggests interaction of the activation pathways. Regulation of secretory response by protein kinase C was investigated with 12-0-tetradecanoyl phorbol-13-acetate (TPA). TPA elevated basal respiration, pepsin release, and acid secretion but inhibited histamine and carbachol stimulation of acid secretion by gastric glands, as measured by [dimethylamino-14C]aminopyrine accumulation. The inhibition of histamine response was specific for protein kinase C activators, occurred after a 20-min lag, and was not reversed by removal of TPA after 3 min of preincubation. TPA pretreatment inhibited acid secretory responses to cholera toxin and forskolin but enhanced the response to cAMP analogues. Cholera toxin and pertussis toxin simulated ADP-ribosylation of 45 and 41 kDa proteins, respectively, in parietal cell membranes. Therefore, both stimulatory (Gs) and inhibitory (Gi) GTP binding proteins of adenylyl cyclase appear to be present in parietal cells. Pretreatment with pertussis toxin attenuated PGE2 but not TPA inhibition of histamine stimulation of aminopyrine accumulation. Thus, the inhibitory effect of TPA does not appear to be associated with an action on Gi. The results with histamine and carbachol suggest that protein kinase C may regulate both cAMP-dependent and -independent stimulation of parietal cell acid secretion.
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PMID:Multiple effects of phorbol ester on secretory activity in rabbit gastric glands and parietal cells. 244 25

The protective effects of three types of pooled human gamma-globulin preparations (intact: GG, S-sulfonated: GGS, and pepsin-treated: GGP) for intravenous use against experimental aerosol infection of mice with Bordetella pertussis have been evaluated. The gamma-globulin preparations GG and GGS showed significant protective activity whereas GGP did not, as evaluated by survival numbers, body weight gains and suppression of leucocytosis. GG and GGS but not GGP also possessed neutralizing activity against leucocytosis-promoting and histamine-sensitizing activities of pertussis toxin (PT). Evaluation of protective activities of GG, GGS and GGP prepared from rabbit gamma-globulin, highly immunized with PT and not containing any anti-F-HA (filamentous or agglutinin antibodies, demonstrated that anti-PT-GG and anti-PT-GGS but not anti-PT-GGP protected against experimental infection by B. pertussis. These studies showed that the protective activity was correlated with anti-PT titre but that the Fc portion of the gamma-globulin molecule is necessary for actual protection against whooping cough by B. pertussis.
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PMID:Protective effects of human gamma-globulin preparations against experimental aerosol infections of mice with Bordetella pertussis. 257 98

The effects of four kinds of human immunoglobulin preparations for intravenous use [pH-4-treated (IG-100), polyethyleneglycol-treated (PEG-G), sulfonated (S-G) and pepsin-treated (Pep-G)] on intracerebral (i.c.) Bordetella pertussis infection in mice, and on B. pertussis vaccine-induced leukocytosis-promoting factor (LPF) and histamine-sensitizing factor (HSF) were compared with those of human immunoglobulin preparation for intramuscular use (GGN). A prophylactic potential against i.c. B. pertussis challenge was demonstrated in IG-100, PEG-G and GGN. A prophylactic potential was also demonstrated in S-G and Pep-G, although to a lesser extent. Neutralizing activity for LPF was in the following order: GGN = IG-100 = PEG-G greater than S-G = Pep-G; for HSF it was as follows: IG-100 greater than PEG-G greater than GGN = S-G greater than Pep-G. There were no significant differences in antibody titers of the various preparations against B. pertussis antigens. These results suggest that the Fc part of the immunoglobulin molecule is important for protecting against i.c. B. pertussis infection and for neutralizing B. pertussis toxins.
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PMID:Effect of human immunoglobulin preparations on experimental Bordetella pertussis infection in mice. 288 Apr 24