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)

Dopamine inhibits and serotonin stimulates adenylate cyclase activity in a neuroblastoma X Chinese hamster brain explant cell line (NCB-20). The inhibition of cyclic AMP accumulation by dopamine was blocked by pretreatment of the cells with pertussis toxin. Carbachol and bradykinin stimulated the accumulation of water-soluble inositol phosphates whereas thyrotropin-releasing hormone, vasopressin, neurotensin, and phenylephrine were without effect. Dopamine and serotonin had no significant effect on carbachol-induced phosphoinositide hydrolysis or the levels of the parent lipids within the membrane. Forskolin induced a much larger stimulation of cyclic AMP than did serotonin, and caused an increase in the levels of phosphatidylinositol-4-phosphate and phosphatidyl inositol-4,5-bisphosphate in the cell membrane.
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PMID:Activation of dopamine receptors does not affect phosphoinositide turnover in NCB-20 cells. 303 93

Growth factors can be divided into two classes which act through distinct signal transduction pathways. One class including epidermal growth factor, platelet derived growth factor and fibroblast growth factor activates receptor tyrosine kinases, and the second class, including thrombin, bombesin, bradykinin and vasopressin activates a phosphoinositide-specific phospholipase C through GTP-binding proteins which can be inactivated by pertussis toxin. In Chinese hamster lung fibroblasts, thrombin-induced mitogenicity seems to correlate well with phospholipase C activation and both events are sensitive to pertussis toxin. Thrombin, like the other mitogens in this class, simultaneously inhibits adenylate cyclase. This involves an inhibitory G protein (Gi), a well established pertussis toxin substrate. The relative contributions of the two signalling pathways to mitogenicity has not been evaluated so far. We report here that the neurotransmitter serotonin (5-hydroxytryptamine), a contracting agent and mitogen for smooth muscle cells, activates phospholipase C, inhibits adenylate cyclase and stimulates DNA synthesis in fibroblasts. These events are sensitive to pertussis toxin. We show that the mitogenicity of 5-hydroxytryptamine can be uncoupled from phospholipase C activation that is mediated by 5-HT2 receptors, but correlates perfectly with inhibition of adenylate cyclase through 5-HT1B receptor. We propose that inhibition of adenylate cyclase or activation of an undefined effector system by Gi is important in 5-hydroxytryptamine induced DNA synthesis and contributes to the strong mitogenicity of the other members of this family of growth factors.
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PMID:Serotonin stimulates DNA synthesis in fibroblasts acting through 5-HT1B receptors coupled to a Gi-protein. 304 68

The addition of bradykinin to NG108-15 cells results in a transient hyperpolarization followed by prolonged cell depolarization. Injection of inositol 1,4,5-trisphosphate or Ca2+ into the cytoplasm of NG108-15 cells also elicits cell hyperpolarization followed by depolarization. Tetraethylammonium ions inhibit the hyperpolarizing response of cells to bradykinin or inositol 1,4,5-trisphosphate. Thus, the hyperpolarizing phase of the cell response may be due to inositol 1,4,5-trisphosphate-dependent release of stored Ca2+ into the cytoplasm, which activates Ca2+-dependent K+ channels. The depolarizing phase of the cell response to bradykinin is due largely to inhibition of M channels, thereby decreasing the rate of K+ efflux from cells and, to a lesser extent, to activation of Ca2+-dependent ion channels and Ca2+ channels. In contrast, injection of inositol 1,4,5-trisphosphate or Ca2+ into the cytosol did not alter M channel activity. Incubation of NG108-15 cells with pertussis toxin inhibits bradykinin-dependent cell hyperpolarization and depolarization. Bradykinin stimulates low Km GTPase activity and inhibits adenylate cyclase in NG108-15 membrane preparations but not in membranes prepared from cells treated with pertussis toxin. Reconstitution of NG108-15 membranes from cells treated with pertussis toxin with nanomolar concentrations of a mixture of highly purified No and Ni [guanine nucleotide-binding proteins that have no known function (No) or inhibit adenylate cyclase (Ni)] restores bradykinin-dependent activation of GTPase and inhibition of adenylate cyclase. These results show that [bradykinin . receptor] complexes interact with No or Ni and suggest that No and/or Ni mediate the transduction of signals from bradykinin receptors to phospholipase C and adenylate cyclase.
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PMID:Bradykinin-activated transmembrane signals are coupled via No or Ni to production of inositol 1,4,5-trisphosphate, a second messenger in NG108-15 neuroblastoma-glioma hybrid cells. 308 91

Incubation of the bovine endothelial cell line, CPAE, with leukotriene D4, leukotriene C4, bradykinin, or the calcium ionophore A23187 results in the release of arachidonic acid metabolites including 6-keto-prostaglandin F1 alpha, the stable metabolite of prostacyclin. Pretreatment of these cells with the pertussis toxin islet-activating protein (IAP) results in a dose-dependent inhibition of the release of arachidonic acid metabolites and prostacyclin in response to leukotriene D4 and leukotriene C4. In contrast, similar responses evoked by bradykinin or ionophore were not significantly altered by the IAP pretreatment of the cells. IAP in the presence of [32P]NAD specifically [32P]ADP-ribosylates a 41-kDa protein in membranes prepared from CPAE cells. Pretreatment of the intact cells with IAP resulted in a dose-dependent inhibition of subsequent 32P labeling of the toxin substrate in the membranes and correlates with the uncoupling of the leukotriene responses. These results suggest that the 41-kDa IAP substrate, presumably a guanine nucleotide regulatory protein, mediates the response of CPAE cells to leukotriene D4 and leukotriene C4, but not to bradykinin or the calcium ionophore.
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PMID:Islet-activating protein inhibits leukotriene D4- and leukotriene C4- but not bradykinin- or calcium ionophore-induced prostacyclin synthesis in bovine endothelial cells. 309 5

The present study has been performed to test for the involvement of pertussis toxin-sensitive GTP-binding proteins (G-proteins) in the cellular transduction of hormone-induced activation of potassium channels. In Madin Darby canine kidney (MDCK) cells, a permanent cell line from dog kidney, epinephrine, acetylcholine, bradykinin, serotonin and ATP hyperpolarize the cell membrane by activation of potassium channels. In cells pretreated with pertussis toxin the hyperpolarizations elicited by either acetylcholine or serotonin are completely abolished; that following epinephrine is blunted and only transient. The hyperpolarizing effects of ATP or bradykinin are not affected by pertussis toxin. Thus, in MDCK cells both pertussis toxin-dependent and -independent mechanisms operate in parallel to enhance the potassium conductance of the cell membrane.
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PMID:Pertussis toxin-dependent and -independent hormonal effects on cultured renal epithelioid cells. 313 57

In human A431 epidermoid carcinoma cells, epidermal growth factor (EGF) rapidly stimulates the breakdown of inositol phospholipids and raises cytoplasmic free [Ca2+]. In this paper, we investigate the action of EGF on inositol phosphate metabolism, and we compare it with the previously described effects of bradykinin on the same cell system [Tilly, van Paridon, Verlaan, Wirtz, de Laat & Moolenaar (1987) Biochem. J. 244, 129-135]. In cells prelabelled with [3H]inositol, EGF slowly but persistently (for at least 30 min) stimulates the formation of [3H]inositol phosphates, whereas bradykinin causes an immediate but transient release of inositol phosphates, which lasts for only a few minutes. The EGF effect is additive to bradykinin stimulation and does not require extracellular Ca2+. In contrast, inositol phosphate formation induced by Ca2+-ionophore A23187 has an absolute requirement for external Ca2+. Treatment of the cells with 12-O-tetradecanoylphorbol 13-acetate completely abolishes the response to EGF and to sub-optimal doses of bradykinin, suggesting a negative-feedback function of protein kinase C. Pretreatment of the cells with pertussis toxin has no effect on inositol phosphate formation induced by either EGF or bradykinin. Unlike bradykinin, EGF stimulates very little accumulation of inositol 1,4,5-trisphosphate, with only a small and rather variable release of Ca2+ from intracellular stores. EGF rapidly but transiently increases inositol 1,3,4-trisphosphate and 1,3,4,5-tetrakisphosphate, but the effects are much smaller than those of bradykinin. In addition, EGF increases both inositol mono- and bis-phosphate. At 10 min after EGF addition, inositol monophosphate, unlike the other inositol phosphates, is still increasing. It is concluded that the EGF-dependent pattern of stimulation is different from that observed in bradykinin-stimulated A431 cells, suggesting that there are separate mechanisms of inositol-lipid hydrolysis involved.
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PMID:Epidermal-growth-factor-induced formation of inositol phosphates in human A431 cells. Differences from the effect of bradykinin. 313 77

Accumulation of inositol phosphates (Ins-Ps, revealed by high performance liquid chromatography), changes of the cytosolic free Ca2+ [( Ca2+]i, revealed by fura-2), membrane potential and ionic currents (revealed by bis-oxonol and patch clamping) were investigated in PC12 cells treated with bradykinin (BK). The phenomena observed were (a) due to the activation of a B2 receptor (inhibitor studies) and (b) unaffected by pertussis toxin, cAMP analogs, and inhibitors of either cyclooxygenase or voltage-gated Ca2+ channels. During the initial tens of s, three interconnected events predominated: accumulation of Ins-1,4,5-P3, Ca2+ release from intracellular stores and hyperpolarization due to the opening of Ca2+-activated K+ channels. Phorbol myristate acetate partially inhibited Ins-1,4,5-P3 accumulation at all [BK] investigated, and the [Ca2+]i increase at [BK] less than 50 nM. In PC12 cells treated with maximal [BK] in the Ca2+-containing incubation medium, Ins-1,4,5-P3 peaked at 10 s, dropped to 20% of the peak at 30 s, and returned to basal within 5 min; the peak increase of Ins-1,3,4-P3 was slower and was variable from experiment to experiment, while Ins-P4 rose for 2 min, and remained elevated for many min thereafter. Meanwhile, influx of Ca2+ from the extracellular medium, plasma membrane depolarization (visible without delay when hyperpolarization was blocked), and increased plasma membrane conductance were noticed. Evidence is presented that these last three events (which were partially inhibited by phorbol myristate acetate at all [BK]) were due to the activation of a cation influx, which was much more persistent than the elevation of the two Ins-P3 isomers. Our results appear inconsistent with the possibility that in intact PC12 cells the BK-induced activation of cation influx is accounted for entirely by the increases of either Ins-1,3,4-P3 or Ins-1,4,5-P3 (alone or in combination with Ins-1,3,4,5-P4), as previously suggested by microinjection studies in different cell types.
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PMID:Generation of inositol phosphates, cytosolic Ca2+, and ionic fluxes in PC12 cells treated with bradykinin. 314 20

The nonapeptide bradykinin (BK) activates sensory neurons and stimulates the transmission of nociceptive information into the CNS. We investigated the effect of this peptide on rat dorsal root ganglion neurons (DRG) grown in vitro. BK stimulated the synthesis of inositol trisphosphate (IP3) and the breakdown of phosphatidylinositol bisphosphate, the synthesis of diacylglycerol, and the release of arachidonic acid from DRG cells. The release of IP3 and arachidonic acid was not inhibited by pretreatment of the cells with pertussis toxin. BK also mobilized intracellular Ca2+ stores in DRG cells as assessed by fura-2-based microfluorimetry. Two types of Ca2+ stores appeared to exist in DRG neurons. One type could be mobilized by caffeine (10(-2) M), and this effect could be blocked by ryanodine in a use-dependent manner. These stores occurred primarily in the cell soma and were virtually absent from cell processes. A second type of store could be mobilized by BK, presumably through the mediation of IP3. These latter stores were distributed equally between the cell soma and processes. Experiments with combinations of caffeine and BK suggested that the stores mobilized by these 2 agents may be separate entities. Both the caffeine and BK sensitive Ca2+ storage sites appeared to participate in buffering a Ca2+ load induced in DRG neurons by cell depolarization. The relevance of these observations to the mechanism of action of BK on sensory neurons is discussed.
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PMID:Regulation of calcium homeostasis in sensory neurons by bradykinin. 318 14

Bradykinin acts on the dorsal root ganglion X neuroblastoma hybrid cell line F-11 to stimulate the rapid elevation of inositol trisphosphate (IP3) and intracellular calcium. We now show an equally rapid release of arachidonyl labeled diacylglycerol (DAG), (243 +/- 32% of control). This first peak of diacylglycerol production was inhibitable by either pretreatment with 200 ng/ml of pertussis toxin overnight or by 10 nM tetradecanoylphorbol acetate (TPA). In addition, a second, more sustained release occurred, plateauing at approximately five minutes (304 +/- 16%). The second peak of DAG was unaffected by these TPA or pertussis pre-incubations. Simultaneous analysis of inositol-labeled phospholipids showed that the initial IP3 and DAG peaks corresponded to initial decreases in phosphoinositides PIP2 and PIP whereas PI increased slightly over this same time period. In contrast, at 5-30 minutes, PIP2 and PIP returned to normal levels, but PI gradually decreased to 75% of control values. Likewise, TPA blocked this early PIP and PIP2 breakdown, but had no effect on the delayed breakdown of monophosphatidylinositol (PI). Bradykinin also induced an equally rapid increase in lysophosphatidyl inositol (lyso-PI) with a peak around 10-30 seconds, and a second more sustained peak after 10 minutes. This production of lyso-PI was not affected by prior treatment with TPA or pertussis toxin. The initial and the sustained phases of diacylglycerol production probably result from different biochemical mechanisms and/or substrates.
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PMID:Bradykinin induces the bi-phasic production of lysophosphatidyl inositol and diacylglycerol in a dorsal root ganglion X neurotumor hybrid cell line, F-11. 325 33

Previous studies have shown that captopril (CP) inhibits ADH-stimulated osmotic water permeability (Pf) in the toad bladder by potentiating endogenous bradykinin (BK). The present studies examine the effect of CP on ADH-stimulated Pf in isolated, perfused rabbit cortical collecting tubules (CCT). CP (10(-4) M) reversibly inhibited Pf, stimulated by maximal concentrations of ADH (10 microU/ml). Pretreatment of CCT's with 5 microM indomethacin, however, abolished the effect of CP. Inhibition of BK production by the kallikrein inhibitors, aprotinin and benzamidine, failed to enhance Pf stimulated by submaximal concentrations of ADH (2.5 microU/ml). Since ADH exerts its effects by activation of adenylyl cyclase (AC), further experiments were performed to identify the site at which CP inhibits this cascade. CP significantly inhibited forskolin (10(-4) M) stimulated Pf; however, it had no effect on cyclic AMP (10(-5) M) stimulated Pf, suggesting that the site of action is on the catalytic subunit or one of the GTP regulatory proteins of AC. To further localize the site of CP's action, CCT's were pre-incubated with pertussis toxin (0.5 microgram/ml) to inactivate the inhibitory, guanosine triphosphate (GTP) regulatory protein, Gi. In these tubules, CP failed to inhibit the action of ADH. We conclude that CP stimulates prostaglandin production which in turn activates Gi and inhibits AC activity. We further suggest that CP stimulates PG's directly, not via BK.
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PMID:Captopril inhibits the hydroosmotic effect of ADH in the cortical collecting tubule. 332 2


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