Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

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

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.
...
PMID:Divergent regulation of beta 2-adrenoceptors and adenylate cyclase in the Cyc- mouse T lymphoma cell line TL2-9. 198 Feb 64

The invasive behaviour of 8 lymphoma cell lines were tested by an in vitro monolayer invasion assay. The metastatic cell lines (TAM 4D1.2, DCH10Sp, TAM 4D6.2, E4 and BWLi) were more invasive than their non-metastatic counterparts (TAS 5C4, BWO and DCH 10). There was a positive correlation between their invasiveness and the PGE1- and forskolin stimulated cellular cAMP levels. Invasiveness and basal cAMP levels could not be correlated. Pretreatment with pertussis toxin (50 ng/ml) for 24 hours provoked did not significantly affect the basal and PGE1-stimulated cAMP levels in all cells. Yet, the toxin catalysed the ADP-ribosylation of 40 kDa components in all cells and provoked a significant increase in the invasiveness of non-metastatic cell lines and a decrease in the invasiveness of metastatic cell lines. These data suggest that the invasiveness of T-lymphoma cell lines might be controlled by a complex interplay between different signal transducing pathways in the membrane, rather than by the intracellular level of cAMP.
...
PMID:Cyclic AMP content and invasive capacity of metastatic variants of the BW-5147 murine T-cell lymphoma. 215 61

The expression of guanine nucleotide-binding proteins (G-proteins) was compared in two clonal lines of rat Nb2 node lymphoma cells, the lactogen-dependent Nb2-11C line and the lactogen-independent Nb2-Sp (spontaneous) line. Both cell lines expressed mRNA transcripts for the G-protein species Gs alpha [1.85 kilobases (kb)], Gi2 alpha (2.35 kb), Go alpha (4.1-4.5 kb), and Gi3 alpha (3.5 kb). Gi1 alpha was not detected. ADP ribosylation in the presence of activated cholera or pertussis toxins and [32P]NAD demonstrated the presence of G-proteins in the membrane fractions of both lines. The cholera toxin substrates consisted of two proteins (mol wt, 46.5 and 43.5 kD), while a single protein (mol wt, 41.5 kD) was ADP ribosylated by pertussis toxin. Surprisingly, the cholera toxin-sensitive proteins (Gs) were at least 20-fold less abundant in the Nb2-Sp cells than in the Nb2-11C cells. Since Gs and Gi2 are associated with the adenylate cyclase system and the regulation of intracellular cAMP, the effects of the cAMP analog, (Bu)2cAMP (dbcAMP), on Nb2-11C and Nb2-Sp cell growth were examined. dbcAMP (100 microM) completely inhibited the growth of lactogen-dependent Nb2-11C cells. The inhibitory effect of dbcAMP was exerted at an early point in the cell cycle, as it also inhibited PRL-stimulated c-myc expression measured 3 h after addition of the mitogen. In contrast, dbcAMP had only minor inhibitory effects on lactogen-independent Nb2-Sp cells, increasing their doubling time from 20 to 30 h and slightly reducing their density at confluence. The inhibitory effect of dbcAMP on both cell lines was reversible. Nb2-11C cells resumed growth after a lag period of approximately 3 days. The recovered cells did not arise from selection of a cAMP-resistant subpopulation, since both they and normal untreated Nb2-11C cells remained equally sensitive to dbcAMP. Similarly, Nb2-Sp cells resumed their normal doubling time upon removal of dbcAMP. The observation that the lactogen-independent Nb2-Sp cell line contained 20-fold less cholera toxin-sensitive Gs protein provides circumstantial evidence that dysfunction of the adenylate cyclase system may be implicated in the autonomous growth of these cells. This possibility is strengthened by the observation that Nb2-Sp cells are markedly less sensitive than the Nb2-11C clone to the growth inhibitory effects of an exogenous cAMP analog.
...
PMID:The role of G-proteins in the mitogenesis of rat lactogen-dependent and lactogen-independent Nb2 lymphoma cells. 215 99

The Nb2 T lymphoma is unique in that these lymphocytes proliferate in response to prolactin as well as in response to interleukin-2. In this study, we have examined the responsiveness of the adenylate cyclase system in Nb2 cells and the role of this signaling system in regulating proliferation and protein phosphorylation. An analog of cAMP inhibited prolactin-stimulated proliferation and blocked a prolactin-induced decrease in protein phosphorylation. Forskolin, a potent activator of adenylate cyclase in T lymphocytes, did not elevate cAMP levels in Nb2 cells and was not an effective inhibitor of prolactin-induced proliferation. In fact, one preparation of forskolin stimulated proliferation of quiescent Nb2 cells. Like forskolin, prostaglandin E2 did not stimulate cAMP production in Nb2 cells even though it increased cAMP in a preparation of rat peripheral blood lymphocytes. Cholera toxin appeared to ADP-ribosylate a stimulatory guanine nucleotide-binding protein in Nb2 cells, but the toxin did not increase intracellular levels of cAMP nor was it a potent anti-mitogenic agent. Pertussis toxin, an agent that can increase cAMP production through suppression of the inhibitory guanine nucleotide-binding protein, exerted only minor anti-proliferative actions on prolactin-stimulated Nb2 cells. These data suggest that cAMP inhibits Nb2 cell proliferation and prolactin-induced changes in protein phosphorylation but that the adenylate cyclase system in our clone of Nb2 cells responds poorly to agents that normally increase cAMP.
...
PMID:Growth and protein phosphorylation in the Nb2 lymphoma: effect of prolactin, cAMP, and agents that activate adenylate cyclase. 216 97

Bordetella pertussis produces a number of virulence determinants which contribute to its pathogenicity. One factor, the adenylate cyclase toxin (ACT), has been suggested to directly penetrate human phagocytes and disrupt their normal function by direct production of intracellular cyclic AMP (cAMP). Experiments evaluating the production of cell-associated ACT in liquid cultures of B. pertussis 504 demonstrated that the greatest activity was observed during mid-log-phase growth. Urea extracts of cells harvested during the time of maximal ACT production have been used to purify the toxin with both biological and enzymatic activities. ACT is a protein with an apparent molecular mass of 220 kDa and an isoelectric point of 7.0. The specific activity of purified ACT is 17,000 mumol of cAMP formed per mg per min. The the biological specific activity of purified ACT is 6,250 nmol of intracellular cAMP formed per mg per min in 2 x 10(6) S49 lymphoma cells per ml. Preparations containing 8 micrograms of ACT completely abrogated the chemiluminescence response of 2 x 10(6) human neutrophils per ml.
...
PMID:Adenylate cyclase toxin of Bordetella pertussis: production, purification, and partial characterization. 222 32

To focus attention on the problem of infant mortality in Lebanon, data were compiled on infant mortality from 1978 to 1986 at the American University of Beirut Medical Center. Causes of death are analyzed for 602 males and 398 females. 54.9% deaths occurred at 1 month of age and 77.4% died within the 1st year. Autopsies were performed on .7%. 37.7% of all neonatal deaths were due to neonatal diseases such as hyaline membrane disease, asphyxia neonatorum, immaturity, necrotizing enterocolitis, hemorrhage, hemolysis, meconium aspiration, and kernicterus. Better prenatal care would reduce this group, or the administration of corticosteroids to the mother 24-48 hours prior to delivery, as well as rapid resuscitation at birth and prevention of the 5 curses: hypoxemia, hypoglycemia, hypothermia, hypotension, and acidosis. Although unavailable in Lebanon, administration of surfactants through an endotracheal tube would also help. Infections constitute 25.1% of deaths; many are preventable through adequate public health measures and strict personal hygiene, i.e., diseases such as sepsis, pneumonia, meningitis, gastroenteritis, hepatitis, encephalitis, and 1-2 cases of the following: diphtheria, measles, peritonitis, tetanus, tuberculosis, cytomegalis inclusion, herpes, parathyphoid, pertussis, poliomyelitis, and shigellosis. Congenital diseases were 21.6%. In utero diagnosis could prevent some diseases and in utero treatment is possible for hydrocephalus and hydronephrosis. Screening programs postnatally could lead to treatment. 5.9% were malignancies such as leukemia, lymphoma, brain tumors, histocytosis, Wilm's tumor, Ewing sarcoma, and Hodgkin's disease. Early diagnosis is critical if mortality is to be reduced in this group, but medical advances are still needed. 2.9% are miscellaneous diseases such as poisoning, rheumatic diseases, marasmus, Reye's syndrome, nephrosis, rickets, and epilepsy. Most of these diseases are preventable, except for rheumatic inflammation of the heart. Recommended necessary steps to reduce infant mortality are: prenatal care, diagnosis and screening, intrauterine surgery; resuscitation and intensive care centers with modern equipment and trained personnel; national vaccination and screening programs; adequate public health measures and hygiene; parental education; and well-equipped hospitals to serve all regardless of income level.
...
PMID:Pediatric mortality: an avoidable tragedy. 251 28

Interaction of specific ligands with TCR initiates a cascade of biochemical events which leads to expression of high affinity IL-2R and subsequent IL-2 secretion. Activation of phospholipase C (PL-C) is considered to be a key event in the initiation of this cascade. However, in addition to this PL-C-dependent pathway, PL-C-independent pathways have been hypothesized. Identification of the steps constituting these PL-C-independent pathways has been difficult because activation of PL-C and the subsequent cascade of events mask the effects of such pathways. Specific inhibitors for PL-C, or mutants defective in, the PL-C pathway would facilitate delineation of alternative activation pathways. We have identified a murine pork insulin/IAd-specific T cell hybridoma, B8P3.11, in which perturbation of the B8P3.11 TCR by either Ag in association with Ia, anti-CD3 antibodies, or a mitogenic lectin does not induce increases in myo-inositol 1,4,5-triphosphate production or cytosolic free calcium, yet it does lead to IL-2 secretion. Treatment of B8P3.11 with pertussis toxin, at concentrations which ADP-ribosylate GTP-binding proteins, inhibits IL-2 secretion. Thus, signal transduction resulting in IL-2 secretion by B8P3.11 likely involves a G protein. In contrast, TCR/ligand interaction activates the PL-C-dependent pathway in LBRM 331A5, a T cell lymphoma. Furthermore, pertussis toxin treatment, which blocks IL-2 secretion by B8P3.11, does not alter IL-2 secretion by LBRM 331A5. However, similar pertussis toxin substrates are present in both cells. Therefore, B8P3.11 T cells should help to elucidate PL-C-independent activation pathways.
...
PMID:IL-2 secretion is pertussis toxin sensitive in a T lymphocyte hybridoma. 252 28

We injected hCG into pseudopregnant rabbits on day 7 of pseudopregnancy and analyzed changes in the components of luteal adenylyl cyclase system in order to determine which components are responsible for altered hormonal responsiveness upon desensitization. hCG-induced desensitization was homologous (loss of responsiveness to LH) early (first 6 h), then became heterologous (partial loss of responsiveness to catecholamines) later (12-48 h). The total number of LH receptors was reduced approximately 30% 3 h after treatment at a time when LH stimulation of adenylyl cyclase activity was not altered. Total LH receptors remained at this level until 24 h, when total receptors were reduced by 88%. While total LH receptor number remained constant, LH-stimulated adenylyl cyclase activity was declining to 57% of the control value at 12 h. Available unoccupied LH receptors were reduced by 96% at 12 h. The affinity of the occupied receptors was reduced 4-fold before down-regulation. The changes in beta-adrenergic receptor number paralleled the changes in catecholamine responsiveness. hCG treatment also altered luteal G-protein function, as assessed by reconstitution of adenylyl cyclase activity in S49 cyc- lymphoma membranes and ADP ribosylation by cholera and pertussis toxins. Isoproterenol (ISO)-reconstituting activities of luteal Gs (the stimulatory G-protein of adenylyl cyclase) were depressed by 65% 12-48 h after hCG treatment, the same time as reduced catecholamine responsiveness. In contrast, NaF-reconstituting activities were at control levels at 12 h and reduced by 55% at 24 and 48 h. Pertussis toxin's ability to ADP ribosylate alpha i 40 was increased 3 and 6 h after treatment, while cholera toxin's ability to ADP ribosylate alpha s 45 was reduced throughout the study period. These studies demonstrate that hCG-induced heterologous desensitization results in a complex series of changes in beta-adrenergic and LH receptors as well as G-protein function, which account for the altered hormonal responsiveness.
...
PMID:Human chorionic gonadotropin-induced heterologous desensitization of rabbit luteal adenylyl cyclase is associated with altered receptor and G-protein function. 253 14

Nitroimidazole derivatives dose-dependently decreased basal and CRF-stimulated ACTH release, basal and GRF-stimulated rat GH release, and basal rat PRL release in primary cultures of rat anterior pituitary cells. In addition, basal and CRF-stimulated mRNA coding for the ACTH precursor were reduced after preincubation with the nitroimidazole derivatives. Miconazole, econazole, isoconazole, clotrimazole, and bifonazole had similar or more pronounced effects on anterior pituitary function compared to ketoconazole, whereas metronidazole and etomidate were less effective. The positive correlation between the number of phenylated side-chains or phenolic rings of the imidazole molecule and the efficacy to inhibit activity on pituitary hormone secretion suggests a structure-activity relationship of these compounds. The effects of the nitroimidazole derivatives on anterior pituitary hormone release and biosynthesis were mediated by cAMP. Thus, basal and CRF-, cholera toxin-, and forskolin-stimulated adenylate cyclase activities in rat anterior pituitary cell membranes determined by cAMP formation were suppressed by the nitroimidazole derivatives. Pertussis toxin did not diminish the nitroimidazole derivative effect on cAMP formation. The adenylate cyclase inhibitory effect of these substances was independent of the presence of GTP in the assay system, underlining a direct effect on the catalytic subunit. In addition, basal and forskolin-stimulated cAMP generation in membranes of S49 lymphoma cyc-variants, which lack a functional Gs protein, was efficiently suppressed (by up to 90%) by the nitroimidazole derivatives. In conclusion, ketoconazole and other nitroimidazole derivatives inhibit anterior pituitary hormone synthesis and secretion apparently by a direct effect on the catalytic subunit of the adenylate cyclase system.
...
PMID:Nitroimidazole derivatives inhibit anterior pituitary cell function apparently by a direct effect on the catalytic subunit of the adenylate cyclase holoenzyme. 254 44

The phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA) and thyroliberin exerted additive stimulatory effects on prolactin release and synthesis in rat adenoma GH4C1 pituicytes in culture. Both TPA and thyroliberin activated the adenylate cyclase in broken cell membranes. When combined, the secretagogues displayed additive effects. TPA did not alter the time course (time lag) of adenylate cyclase activation by hormones, guanosine 5'-[beta,gamma-imino]triphosphate or forskolin, nor did it affect the enzyme's apparent affinity (basal, 7.2 mM; thyroliberin-enhanced, 2.2 mM) for free Mg2+. The TPA-mediated adenylate cyclase activation was entirely dependent on exogenously added guanosine triphosphate. ED50 (dose yielding half-maximal activation) was 60 microM. Access to free Ca2+ was necessary to express TPA activation of the enzyme, however, the presence of calmodulin was not mandatory. TPA-stimulated adenylate cyclase activity was abolished by the biologically inactive phorbol ester, 4 alpha-phorbol didecanoate, by the protein kinase C inhibitor polymyxin B and by pertussis toxin, while thyroliberin-sensitive adenylate cyclase remained unaffected. Experimental conditions known to translocate protein kinase C to the plasma membrane and without inducing adenylate cyclase desensitization, increased both basal and thyroliberin-stimulated enzyme activities, while absolute TPA-enhanced adenylate cyclase was maintained. Association of extracted GTP-binding inhibitory protein, Gi, from S49 cyc- murine lymphoma cells with GH4C1 cell membranes yielded a reduction of basal and hormone-stimulated adenylate cyclase activities, while net inhibition of the cyclase of somatostatin was dramatically enhanced. However, TPA restored completely basal and hormone-elicited adenylate cyclase activities in the Gi-enriched membranes. Finally, TPA completely abolished the somatostatin-induced inhibition of adenylate cyclase in both hybrid and non-hybrid membranes. These data suggest that, in GH4C1 cells, protein kinase C stimulation by phorbol esters completely inactivates the n alpha i subunit of the inhibitory GTP-binding protein, leaving the n beta subunit functionally intact. It can also be inferred that thyroliberin conveys its main effect on the adenylate cyclase through activation of the stimulatory GTP-binding protein, Gs.
...
PMID:Protein kinase C stimulates adenylate cyclase activity in prolactin-secreting rat adenoma (GH4C1) pituicytes by inactivating the inhibitory GTP-binding protein Gi. 256 96


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

---