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)

An adrenal cGMP-stimulated phosphodiesterase (cGS-PDE) has been shown to mediate atrial natriuretic peptide (ANP)-induced reductions in aldosterone secretion and cAMP levels in primary bovine glomerulosa cells. High concentrations of cGS-PDE have been localized to the zona glomerulosa cell layer of the adrenal cortex using biochemical and immunological techniques. Immunoblot analysis using an affinity-purified, isozyme-specific antiserum revealed a single band that comigrated with a purified cGS-PDE (105 kDa) (1) and that was most highly concentrated in the outermost 1-2 mm of the cortex, representing the capsule and zona glomerulosa regions. Greater than 90% of the overall phosphodiesterase activity present in tissue extracts prepared from these regions was immunoprecipitated using a solid-phase monoclonal antibody reagent, indicating the cGS-PDE as the predominant phosphodiesterase isozyme. Immunohistochemical staining experiments of frozen thin sections of intact adrenal tissue revealed that the cGS-PDE present in this region was localized in the glomerulosa cells themselves. The role of this isozyme as a mediator of ANP-induced decreases in intracellular cAMP concentrations and aldosterone production was tested in primary cultures of bovine adrenal glomerulosa cells. In cells stimulated by ACTH, ANP treatment produced dose-dependent reductions in aldosterone secretion and cellular cAMP content over the same concentration range. Increases in aldosterone production elicited by three cell-permeable cAMP derivatives (8-bromo-cAMP, 8-p-chlorophenylthio-cAMP, and N6-2'-O-dibutyryl-cAMP) were antagonized by ANP, indicating a site of action distal to adenylate cyclase for this hormone. Because the relative magnitude of the ANP effect differed depending upon the derivative used, the three derivatives were compared with respect to their relative rates of in vitro hydrolysis by adrenal cGS-PDE. A positive correlation between their rates of hydrolysis and the degree to which the steroidogenic response produced by these derivatives was antagonized by ANP was demonstrated, further suggesting an ANP-induced activation of the cGS-PDE as being responsible for this effect. The possible contribution of an additional pathway mediated by an inhibitory guanine nucleotide binding regulatory protein (Gi) acting on adenylate cyclase was tested by pretreatment of primary glomerulosa cells with pertussis toxin. Levels of pertussis toxin sufficient to inhibit subsequent in vitro ribosylation did not significantly alter the ANP effect on aldosterone production, although a partial reduction in the ANP effect on cAMP levels was observed.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:High concentrations of a cGMP-stimulated phosphodiesterase mediate ANP-induced decreases in cAMP and steroidogenesis in adrenal glomerulosa cells. 184 62

Cultured bovine endothelial cells (EC) have specific receptors for endothelin (ET)-3 functionally coupled to phosphoinositide breakdown. We studied whether ET-3 stimulates synthesis of nitric oxide (NO), an endothelium-derived relaxing factor that activates soluble guanylate cyclase in EC, and whether the ET-3-induced NO formation involves G-proteins. ET-3 dose-dependently stimulated production of intracellular cGMP in EC, of which effects were abolished by pretreatment with NG-monomethyl L-arginine, an inhibitor of NO synthesis, and methylene blue, an inhibitor of soluble guanylate cyclase. The stimulatory effects of ET-3 on cGMP production, inositol trisphosphate formation and increase in cytosolic free Ca2+ concentration were similarly blocked by pretreatment with pertussis toxin (PTX). These data suggest that ET-3 induces synthesis of NO mediated by phosphoinositide breakdown via PTX-sensitive G-protein in EC.
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PMID:Endothelin-3 stimulates production of endothelium-derived nitric oxide via phosphoinositide breakdown. 184 38

ANP increases cellular cGMP content in cultured hepatocytes and decreases Ca2(+)-inflow in a concentration- and time-dependent manner which explains a beneficial effect on hypoxia cell injury (25). Both observations are mimicked by SNP and 8-Br-cGMP and blocked by Ly 83583 indicating a cGMP-mediated mechanism. The protective effect was also inhibited by Pertussis Toxin (PT) without lowering the elevated cGMP-level. But PT in combination with ANP leads to a higher Ca2(+)-inflow. Stimulated Na(+)-inflows are also be lowered by ANP. Here, neither SNP can mimick nor PT can inhibit this effect. Our results now indicate that the beneficial effect by ANP at the cellular level is mediated through cGMP which decreases calcium-inflow. ANP seems to control Ca2(+)-channels direct via a PT-sensitive G-protein and indirect by a cGMP-mediated mechanism and Na(+)-channels cGMP-independent through a PT-insensitive G-protein, thus preventing cells on hypoxia and oxygen radicals.
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PMID:The protective effect of atrial natriuretic peptide (ANP) on cells damaged by oxygen radicals is mediated through elevated CGMP-levels, reduction of calcium-inflow and probably G-proteins. 184 48

Signal transduction for the characteristic long-term desensitization of glutamate receptors in Purkinje cells was investigated with wedge recordings from rat cerebellar slices. Long-term desensitization was induced specifically in the AMPA-selective subtype of glutamate receptors following brief exposure to 100 microM quisqualate. It was abolished either by treatment of the rat with pertussis toxin or by perfusion of a slice with BAPTA-AM, L-NMMA, hemoglobin, or inhibitor of PKG. Brief application of AMPA alone did not cause desensitization, but in combination with t-ACPD, sodium nitroprusside, or 8-bromo-cGMP, AMPA produced desensitization similar to that induced by quisqualate. These results indicate that the desensitization arises from activation of AMPA receptors in association with activation of metabotropic glutamate receptors, the latter leading to Ca2+ elevation to nitric oxide (NO) production to cGMP synthesis, and eventually to activation of PKG.
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PMID:Messengers mediating long-term desensitization in cerebellar Purkinje cells. 196 3

The present study was carried out to evaluate the effects of biologically active atriopeptin II (APII) in synchronously contracting monolayer cultures of rat ventricular myocytes. The effects of 10 nM APII on Ca influx, contractile behavior and cyclic nucleotide content of the cells were measured. Applied acutely APII had no effect on Ca influx. There was however a time-dependent effect such that after 30 min Ca influx (pmol/cm2/s) had declined from a control (mean +/- S.E.M.) of 1.53 +/- 0.16 to 1.02 +/- 0.07 (P less than 0.001; n = 6). There was parallel decline in both the magnitude and velocity of cell edge motion which was maximal in 30 min at which time cell edge motion measured 65.3 +/- 4.4% of control. Treatment with APII for 30 min decreased cAMP (pmol/mg protein) from 5.35 +/- 0.17 to 2.86 +/- 0.24 (P less than 0.001; n = 5). At the same time cGMP (pmol/mg protein) increased from 0.86 +/- 0.21 to 2.14 +/- 0.33 (P less than 0.001; n = 5). Further studies elucidated the fact that the decline in Ca influx and contractile behavior was dependent on the decrease in cAMP rather than the increase in cGMP. Pre-treatment of the cells with 5 ng/ml of pertussis toxin to ADP-ribosylate the Gi protein abolished the effects of APII on cAMP, Ca influx and contractile behavior. The results indicate that in myocardial cells, as in other cells, APII stimulates guanylate cyclase and inhibits adenylate cyclase. The resultant fall in cAMP decreases Ca influx and negatively influences the contractile behavior of the cells.
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PMID:Effect of atriopeptin II on Ca influx, contractile behavior and cyclic nucleotide content of cultured neonatal rat myocardial cells. 196 67

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

This study tests the hypothesis that atrial natriuretic factor (ANF) and C-ANF(4-23)-NH2 (C-ANF) augment cGMP generation and inhibit both cAMP generation and depolarization-induced catecholamine release in nerve growth factor treated pheochromocytoma cells by a pertussis toxin (PTX)-sensitive mechanism. Synthetic rat ANF(99-126) and the clearance receptor antagonist C-ANF (10(-12)-10(-9) M) inhibited basal and 5 microM vasoactive intestinal peptide (VIP)-induced cAMP generation in a concentration-dependent manner. These actions of ANF and C-ANF were blocked by 12-18 h pretreatment with PTX (100 ng/ml), suggesting ANF receptor coupling to adenylate cyclase via an inhibitory guanine nucleotide-binding protein. Both ANF (10(-11)-10(-9) M) and C-ANF (10(-11)-10(-8) M) also inhibited K(+)-induced catecholamine release in a concentration-dependent manner. ANF (10(-11)-10(-8) M) increased cGMP generation in a concentration-dependent manner but C-ANF did not. The accumulation of cGMP in response to ANF was not altered by treatment with PTX. Therefore, PTX dissociated the increased concentrations of cGMP from the ANF-mediated depression of evoked catecholamine release. C-ANF also dissociated elevations in cGMP concentrations from an ANF-mediated attenuation of evoked catecholamine release. The results of this study indicate that ANF inhibits adrenergic neurotransmission independent of guanylate cyclase.
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PMID:Neuromodulatory effects of atrial natriuretic factor are independent of guanylate cyclase in adrenergic neuronal pheochromocytoma cells. 197 29

Treatment of rat thoracic aortic smooth muscle cells (A-10) with sodium fluoride (NaF) resulted in inhibition of beta-adrenergic agonist--and forskolin-induced cAMP and ANF-induced cGMP accumulation and stimulation of diacylglycerol (DAG) accumulation. The concentration of NaF and treatment times required to mediate these inhibitory effects were similar to those observed for stimulation of DAG accumulation. Treatment of the cells with NaF also resulted in a loss of [3H]phorbol dibutyrate (PDBu) binding in the cytosolic portion of the cells. In addition, pre-treatment of the cells with NaF resulted in an increase in the adenylate cyclase activity. Pertussis toxin (PT) pre-treatment of the cells did not significantly affect NaF-mediated effects. Pre-treatment of the cells with protein kinase C (PKC) inhibitor staurosporin partially reversed NaF-mediated inhibition of cyclic nucleotides accumulation. These data suggest that inhibition of the formation of agonist-induced cyclic nucleotides by NaF may be due to the formation of DAG and cAMP which lead to the activation of PKC and cAMP-PK, resulting in phosphorylation of key regulatory protein(s) in the cyclic nucleotides pathway.
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PMID:Possible involvement of protein kinase C and cyclic AMP-dependent protein kinase in the sodium fluoride-mediated inhibition of cyclic nucleotide accumulation in smooth muscle cells. 208 Oct 95

The effect of pertussis toxin (PTX) and the cyclic GMP lowering agent LY83583 on the relaxatory response induced by glyceryl trinitrate (GTN), isosorbide dinitrate (ISDN), isosorbide-5-mononitrate (IS-5-MN) and sodium nitroprusside (SNP) in bovine mesenteric artery (BMA) was investigated. Pretreatment with PTX (100 ng/ml; 2 hr induced a 100-fold right shift of the concentration-effect curve for GTN, while no effect on the relaxatory response elicited by ISDN, IS-5-MN or SNP was seen. The relaxatory effect of all the substances tested was markedly reduced by LY83583 (10 microM). The basal cGMP level as well as the GTN induced increase in cGMP were markedly reduced when BMA was exposed to LY83583. The substance also reduced the activation of soluble guanylate cyclase by SNP. Based on the different sensitivity towards PTX it is suggested that GTN induces vascular smooth muscle relaxation by a partly different mechanism than ISDN, IS-5-MN and SNP. As far as the GTN induced relaxation is concerned the sensitivity towards PTX indicates the involvement of regulatory component, possibly a G-protein. However, cyclic GMP seems to play a crucial role in mediating the relaxatory response of all the substances tested since the cGMP-lowering agent LY83583 markedly inhibited the relaxant response induced by all the vascular relaxant agents investigated.
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PMID:Relaxation of bovine mesenteric arteries by glyceryl trinitrate and other nitro-compounds: evidence for partly different mechanisms of action. 212 85

The inhibitory nucleotide-regulatory protein (Gl) has been shown to lose its adenylate cyclase inhibitory effect upon treatment with pertussis toxin. To find out whether a pertussis sensitive mechanism is involved in the regulation of the cGMP-system, bovine mesenteric arteries were incubated in buffer containing pertussis toxin, and the relaxation and intracellular cGMP accumulation induced by different groups of vasodilating agents were studied. The present results show a pertussis toxin induced decrease in relaxation as well as a decrease in the cGMP-elevation induced by the endothelium dependent vasodilators acetylcholine and calcium ionophore A 23187. Arteries treated with atrial natriuretic peptide showed no alterations in relaxation or cGMP content after incubation with pertussis toxin. A 40 kD soluble ribosylation substrate for pertussis toxin was identified in bovine mesenteric artery. These results suggest that a pertussis toxin sensitive mechanism is involved in the vasodilating mechanism of acetylcholine and calcium ionophore A 23187, while no evidence for such a mechanism could be found regarding the vasodilatory action of atrial natriuretic peptide.
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PMID:Effects of pertussis toxin on vasodilation and cyclic GMP in bovine mesenteric arteries and demonstration of a 40 kD soluble protein ribosylation substrate for pertussis toxin. 215 64


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