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)

Interleukin-3 stimulates the survival and proliferation of the FDCP-Mix 1 multipotent stem cell line. We have investigated the possible involvement of a guanyl nucleotide regulatory (G) protein(s) in the IL-3 stimulated proliferative response. We report here that pertussis toxin (PT) can partially inhibit IL-3 stimulated DNA synthesis and that this inhibition is bypassed by TPA. The ADP-ribosylation of the PT substrate G protein in vivo is complete in 2 hours without concomitant inhibition of IL-3 stimulated hexose transport or Na+/H+ exchange. When loaded into FDCP-Mix 1 cells fluoroaluminate and GTP-gamma-S, which can directly activate G proteins, are not capable of mimicking the effects of IL-3. Evidence is also presented that IL-3 does not stimulate a membrane-bound high affinity GTPase activity in the FDCP-Mix 1 cell line. These data suggest that a PT substrate G protein(s) can influence the IL-3 signalling cascade in an indirect or permissive manner, but that the IL-3 receptor does not directly couple to a PT substrate G protein.
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PMID:IL-3 stimulated haemopoietic stem cell proliferation: evidence for G protein independent mitogenic signalling events. 132 14

Basic fibroblast growth factor (bFGF) stimulates mitogenesis of Balb/c 3T3 fibroblast cells. This stimulation may be mediated by multiple signal pathways as it is accompanied by the formation of inositol phosphates, activation of PKC (protein kinase C) and a decrease in intracellular cAMP levels. The multiple positive and negative pathways implicated for FGF-induced mitogenesis may interact and each may contribute in varying degrees to the final cellular response. At least two types of G-proteins may be involved in the intracellular signalling pathways of FGF. Pertussis toxin blocks FGF and TPA (12-O-tetradecanoylphorbol-13-acetate) induced. PKC-mediated mitogenesis and also the associated fall in intracellular cAMP levels. However, pertussis toxin has no effect upon FGF-induced inositol phosphates formation. Thus, inhibition of mitogenesis by pertussis toxin may involve pertussis toxin sensitive G-proteins which may affect at least two separate putative signal pathways involving adenylate cyclase and protein kinase C. Pertussis toxin insensitive G-proteins may also be involved in coupling the FGF receptor to phosphoinositidase C.
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PMID:Studies on the mechanisms of signalling and inhibition by pertussis toxin of fibroblast growth factor-stimulated mitogenesis in Balb/c 3T3 cells. 165 71

The mechanisms of muscarinic receptor-linked increase in cAMP accumulation in SH-SY5Y human neuroblastoma cells has been investigated. The dose-response relations of carbachol-induced cAMP synthesis and carbachol-induced rise in intracellular free Ca2+ were similar. The stimulated cAMP synthesis was inhibited by about 50% when cells were entrapped with the Ca2+ chelator BAPTA or in the presence of the protein kinase C (PKC) inhibitor staurosporine. Production of cAMP could be induced also by the Ca2+ ionophore, ionomycin and by TPA, an activator of PKC. When added together TPA and ionomycin had a synergistic effect. When cAMP synthesis was activated with cholera toxin, PGE1 or PGE1 + pertussis toxin carbachol stimulated cAMP production to the same extent as in control cells. Ca2+ and protein kinase C thus seem to be the mediators of muscarinic-receptor linked cAMP synthesis by a direct action on adenylate cyclase.
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PMID:Muscarinic receptor-linked elevation of cAMP in SH-SY5Y neuroblastoma cells is mediated by Ca2+ and protein kinase C. 165 8

Heterologous expression of the rat 5-HT1A receptor in stably transfected GH4C1 rat pituitary cells (clone GH4ZD10) and mouse Ltk- fibroblast cells (clone LZD-7) (Albert, P.R., Zhou, Q.-Y., VanTol, H.H.M., Bunzow, J.R., and Civelli, O. (1990) J. Biol. Chem. 265, 5825-5832) was used to characterize the cellular specificity of signal transduction by the 5-HT1A receptor. We demonstrate that the 5-HT1A receptor, acting via pertussis toxin-sensitive G proteins, can change its inhibitory signaling phenotype and become a stimulatory receptor, depending on the cell type, differentiation state, or intracellular milieu of the cell in which it is expressed. When expressed in pituitary GH4ZD10 cells, activation of 5-HT1A receptors decreased both basal and vasoactive intestinal peptide-enhanced cAMP accumulation and blocked (+/-)-Bay K8644-induced influx of calcium, inhibitory responses which are typical of neurons which endogenously express this receptor. Similarly, 5-hydroxytryptamine (5-HT) also inhibited adenylyl cyclase in fibroblast LZD-7 cells, reducing the forskolin-induced enhancement of cAMP levels by 50%, but did not alter basal cAMP levels. In contrast to GH4ZD10 cells, where 5-HT had no effect on basal or thyrotropin-releasing hormone-induced phosphatidylinositol turnover, 5-HT enhanced the accumulation of inositol phosphates and induced a biphasic increase in [Ca2+]i in LZD-7 cells. These dominant stimulatory actions of 5-HT, as well as the inhibitory effects, were absent in untransfected cells and displayed the potency and pharmacological specificity of the 5-HT1A receptor, indicating that the 5-HT1A subtype coupled to both inhibitory and stimulatory pathways in the fibroblast cell. The actions of 5-HT in GH and L cells were blocked by 24-h pretreatment with pertussis toxin, suggesting that inhibitory G proteins (Gi/G(o)) mediate both inhibitory and stimulatory signal transduction of the 5-HT1A receptor. However, the 5-HT-induced stimulatory pathway in fibroblasts was blocked selectively by acute (2-min) pretreatment with TPA, an activator of protein kinase C. This action of protein kinase C was potentiated by activation of protein kinase A, indicating that the expression of the stimulatory pathway of the 5-HT1A receptor in LZD-7 cells is modulated by second messengers.
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PMID:Cell-specific signaling of the 5-HT1A receptor. Modulation by protein kinases C and A. 166 Aug 81

Calcitonin (CT) is a well-known inhibitor of osteoclastic bone resorption both in vivo and in vitro. The effect is mediated by activation of adenylate cyclase and subsequent increased levels of cyclic AMP (cAMP). We report here that CT-induced (30 nmol/liter) accumulation of cAMP in cultured neonatal mouse calvaria is enhanced two-fold by 12-O-tetradecanoylphorbol-13-acetate (TPA; 100 nmol/liter) and phorbol 12,13-dibutyrate (PDBU; 100 nmol/liter), two protein kinase C (PKC)-activating phorbol esters, whereas phorbol 13-monoacetate (phorb-13; 100 nmol/liter), a related compound that does not activate PKC, has no effect. The ability of TPA and PDBU to enhance CT-stimulated cAMP accumulation was obtained also in the presence of indomethacin (1 mumol/liter). Kinetic studies revealed that TPA enhanced the cAMP response to CT at all the time points at which CT had a significant effect per se and that TPA did not alter the time-course of the cAMP response to CT. Treatment with pertussis toxin (100 ng/ml) enhanced cAMP response to parathyroid hormone (10 nmol/liter) and prostaglandin E2, but not to CT. From these data it is concluded that PKC, but not pertussis toxin-sensitive guanyl nucleotide-binding proteins (G-proteins), can interact with and modify the signal transducing system for CT in osteoclasts.
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PMID:Effects of phorbol esters and pertussis toxin on calcitonin-stimulated accumulation of cyclic AMP in neonatal mouse calvarial bones. 166 13

Following exposure to a number of hormones, the cell membrane in Madin-Darby Canine Kidney (MDCK) cells is hyperpolarized by increase of intracellular calcium activity. The present study has been performed to elucidate the possible role of calmodulin in the regulation of intracellular calcium activity and cell membrane potential. To this end trifluoperazine has been added during continuous recording of cell membrane potential or intracellular calcium. Trifluoperazine leads to a transient increase of intracellular calcium as well as a sustained hyperpolarization of the cell membrane by activation of calcium sensitive K+ channels. Half-maximal effects are observed between 1 and 10 mumol/L trifluoperazine. A further calmodulin antagonist, chlorpromazine, (50 mumol/L), similarly hyperpolarizes the cell membrane. The effects of trifluoperazine are virtually abolished in the absence of extracellular calcium. Pretreatment of the cells with either pertussis toxin or phorbol-ester TPA does not interfere with the hyperpolarizing effect of trifluoperazine. In conclusion, calmodulin is apparently involved in the regulation of calcium transfer across the cell membrane but not in the stimulation of K+ channels by intracellular calcium.
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PMID:Effect of trifluoperazine on renal epithelioid Madin-Darby canine kidney cells. 188 Jan 56

The effect of 12-tetradecanoyl phorbol 13-acetate on the GTPase activity of Gi was investigated. Treatment with TPA did not alter basal GTPase activity of membranes or the stimulatory effect of prostaglandin E1 (putatively via Gs). In contrast, the phorbol ester markedly diminished stimulation of GTPase by agents whose receptors are coupled to Gi such as epinephrine (alpha-adrenergic action), platelet activating factor or thrombin. Pertussis toxin catalyzed ADP-ribosylation was also decreased in membranes from TPA-treated platelets as compared to the controls. It is suggested that the alteration in the hormonal activation of the GTPase activity of Gi is secondary to a perturbation in the receptor-Gi interaction.
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PMID:Activation of protein kinase C inhibits hormonal stimulation of the GTPase activity of Gi in human platelets. 190 Apr 75

To gain insight into the mechanisms that could account for the augmentation of cellular reactivity in primary hypertension, we have examined some of the biochemical events which are implicated in the transmission of mitogenic signal as well as in cell reactivity. This study focussed on phospholipase C, protein kinase C and GTP-binding proteins (G-proteins), in response to thrombin or arginin-vasopressin (AVP). Cultured fibroblasts prepared from the adventitia of thoracic aorta of spontaneously hypertensive rat (SHR) were used as cell models and were compared with fibroblasts prepared from controls Wistar-Kyoto (WKY) rats. The mitogenicity of each agonist was estimated by measuring the incorporation of 3H-thymidine into the newly synthesized DNA. The agonist-induced phospholipase C activity was evaluated by measuring the production of 3H-inositol phosphates in cells prelabeled with 3H-inositol. The influence of protein kinase C and that of G proteins on the mitogenesis in cells stimulated by thrombin or AVP was determined by pretreating cells with phorbol 12-myristate, 13-acetate (TPA) and pertussis toxin, respectively. Kinetics and dose response studies have demonstrated that in response to thrombin and AVP, the phospholipase C activity and the incorporation of 3H-thymidine were significantly higher in the fibroblasts derived from SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Activation mechanisms by thrombin and vasopressin of fibroblasts in spontaneously hypertensive rats]. 195 75

The hypothesis that Gi might be involved in the alpha 1-adrenergic, protein kinase C (PKC)-mediated amplification of beta-adrenergic cyclic AMP stimulation in rat pinealocytes was investigated. Treatment of pinealocytes with a high concentration of pertussis toxin (500 ng/ml, 18 h) almost completely (approximately 95%) inactivated two cell membrane G-proteins (kDa 40.7 and 39.8) judged by back ADP-ribosylation of pinealocyte membrane proteins. However, this treatment failed to inhibit either the beta-adrenergic (isoprenaline, ISO 10(-6) M), alpha 1-plus beta-adrenergic (noradrenaline, NA 10(-5) M) or beta-adrenergic plus 12-O-tetradecanoylphorbol 13-acetate (TPA 10(-7) M) induced stimulation of cyclic AMP or cyclic GMP. These results suggest that alpha 1-adrenergic potentiation of beta-adrenergic stimulation of cyclic AMP and cyclic GMP does not involve a pertussis toxin-sensitive G-protein.
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PMID:Pertussis toxin does not inhibit alpha 1-adrenergic potentiation of beta-adrenergic stimulation of cyclic AMP accumulation in rat pinealocytes. 197 Jul 31

The radiation leukemia virus-induced murine Cyc- T lymphoma cell line TL2-9 expressed one homogeneous population of beta 2-adrenoceptors based on competition curves of [125I]cyanopindolol with the specific antagonist ICI 118.551 and three beta-adrenergic agonists. These receptors were uncoupled from adenylate cyclase due to the absence of Gs. The catalytical unit was directly stimulated by MnCl2, forskolin, and even more markedly in the simultaneous presence of both reagents. In contrast, the enzyme was inhibited in the presence of Gpp[NH]p, probably through interaction with Gi. Indeed, this inhibitory effect was constrained by preincubating cells in the presence of pertussis toxin and a 41 kDa protein was specifically ADP-ribosylated in the presence of the toxin. This cell line was therefore analogous to the Cyc- cell line derived from the murine S49 lymphoma cell line. When added to the culture medium, butyrate (2 mM) induced beta 2-adrenoceptors, the expression of these uncoupled receptors depending on protein synthesis, as judged by inhibitory effects of cycloheximide. In contrast, dBcAMP (1 mM) and TPA (tumor-promoting agent phorbol ester) increased the rate of disappearance of beta 2-adrenoceptors. Butyrate, dBcAMP and TPA systematically decreased adenylate cyclase activity. Besides, TPA (but neither butyrate nor dBcAMP) reduced the efficacy of Gpp[NH]p in inhibiting adenylate cyclase, suggesting a proportionately higher alteration of Gi. We conclude that beta 2-adrenoceptors, uncoupled from adenylate cyclase, are regulated independently from the catalytical unit and Gi, in this Cyc- T lymphoma cell line.
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PMID:Divergent regulation of beta 2-adrenoceptors and adenylate cyclase in the Cyc- mouse T lymphoma cell line TL2-9. 198 Feb 64


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