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)

Endogenous ADP-ribosylation of proteins was measured in homogenates, membranes, and cytosol from rat brain regions. Several proteins were ADP-ribosylated in homogenates, especially a 49 kDa protein. Sodium nitroprusside, a source of nitric oxide, particularly enhanced the ADP-ribosylation of 47 kDa and 39 kDa proteins. Levels of basal and sodium nitroprusside-stimulated ADP-ribosylated proteins were similar, but not identical, in homogenates from the cerebral cortex, hippocampus, striatum, thalamus and cerebellum. In neonatal cerebral cortex, ADP-ribosylation of an additional 110 kDa protein was detected and this was also enhanced by sodium nitroprusside. ADP-ribosylation of the 110 kDa protein was evident one and two days after birth, but not at five days and later. Each protein demonstrated unique sensitivities to sodium nitroprusside and rates of ADP-ribosylation. Cyclic GMP did not mimic the effects of sodium nitroprusside. Mg2+ inhibited ADP-ribosylation of the 49 kDa and 47 kDa proteins but had a smaller effect on the 39 kDa protein. ADP-ribosylation in the cytosol predominantly affected only a single protein of 39 kDa, and this was stimulated by sodium nitroprusside and by addition of cofactors necessary for activation of nitric oxide synthase. Several proteins in membranes were ADP-ribosylated and the 49 and 47 kDa proteins were released from the membranes coincidentally with ADP-ribosylation. The predominate substrates of endogenous ADP-ribosylation did not appear to be substrates for pertussis toxin-induced ADP-ribosylation. These and previously published results indicate that nitric oxide generated from sodium nitroprusside or endogenous sources may have modulatory effects through regulation of the endogenous ADP-ribosylation of proteins.
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PMID:Modulation of endogenous ADP-ribosylation in rat brain. 133 43

Nitric oxide-releasing compounds were shown to activate an ADP-ribosyltransferase activity in the cytosol of Dictyostelium discoideum. The enzyme ADP-ribosylated a cytosolic protein of approximately 41 kDa, p41. Neither cGMP nor GTP and its analogues affected this ADP-ribosylation. p41 differs from other substrates ADP-ribosylated by cholera, pertussis, or diphtheria toxins. Treatment of ADP-ribosylated p41 with snake venom phosphodiesterase released adenosine 5'-monophosphate, indicating a mono-ADP-ribose-protein linkage. This linkage was stable to neutral hydroxylamine but was sensitive to mercury ions and iodomethane, suggesting an attachment to a cysteine residue. Treatment of intact cells with nitric oxide-releasing compounds appeared to stimulate the ADP-ribosylation of p41 and this modification was reversible.
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PMID:Nitric oxide stimulates the ADP-ribosylation of a 41-kDa cytosolic protein in Dictyostelium discoideum. 135 80

To determine whether direct stimulation of endothelial G-proteins causes relaxations of the underlying vascular smooth muscle, the effects of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and sodium fluoride were studied in porcine coronary arteries and endothelial cells. Isometric tension was measured in coronary rings contracted with prostaglandin F2 alpha. GTP gamma S (in the presence of saponin) and sodium fluoride (in the presence of AlCl3) relaxed rings with, but not those without endothelium. The responses were inhibited by nitro-L-arginine and pertussis toxin. In membrane fractions of coronary endothelial cells, GTP gamma S and sodium fluoride inhibited the ADP-ribosylation of G-proteins catalyzed with [32P]-NAD and pertussis toxin. These data suggest that direct stimulation of G-proteins in endothelial cells by GTP gamma S and sodium fluoride causes a pertussis toxin-sensitive relaxation which may be attributed to the release of nitric oxide.
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PMID:Guanosine 5'-O-(3-thiotriphosphate) causes endothelium-dependent, pertussis toxin-sensitive relaxations in porcine coronary arteries. 144 86

Experiments were designed to determine whether chronic increases in arterial blood flow alter production of or response to nitric oxide and endothelin. Canine femoral arteries proximal to an arteriovenous fistula- and from the contralateral sham-operated blood vessels were removed, cut into rings, and suspended for measurement of isometric force in organ chambers. The remainder of the artery was homogenized for measurement of endothelin content by radioimmunoassay. NG-monomethyl-L-arginine (10(-4) M) caused concentration-dependent increases in tension only in fistula-operated arteries. Endothelium-dependent relaxations to acetylcholine and BHT-920 were greater in fistula- compared with sham-operated arteries. These differences were reduced by the arginine analogue. Pertussis toxin (100 ng/ml) inhibited relaxations to acetylcholine only in fistula-operated arteries and to BHT-920 only in sham-operated arteries. Contractions to endothelin-1 were greater in fistula- compared with sham-operated arteries. These results suggest that chronic increases in blood flow enhance the tonic and receptor-stimulated production of nitric oxide and its release by receptors coupled to pertussis toxin-sensitive guanine nucleotide regulatory proteins. Furthermore, chronic increases in blood flow may either inhibit the production of endothelin or promote its depletion from endothelial cells while simultaneously increasing the sensitivity of the smooth muscle to its contractile effects.
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PMID:Modulation of NO and endothelin by chronic increases in blood flow in canine femoral arteries. 163 49

Chronic treatment with estrogens enhances some endothelium-dependent relaxations. Whether or not progesterone would exert a similar effect is unknown. Experiments were designed to determine the effect of chronic treatment with progesterone on endothelium-dependent responses. Adult female dogs were ovariectomized and pellets containing carrier substance, estrogen, progesterone, or estrogen plus progesterone were implanted subcutaneously. After 14-21 days coronary arteries were removed, cut into rings, and suspended for the measurement of isometric force in organ chambers in the presence of indomethacin. Endothelium-dependent relaxations to ADP, bradykinin, or the calcium ionophore did not differ among groups. However, relaxations to acetylcholine and to the alpha 2-adrenergic agonist BHT-920 were greater in the estrogen-treated group than in the estrogen plus progesterone-treated group. In rings without endothelium, relaxations to nitric oxide and isoproterenol did not differ among groups. However, relaxations of the smooth muscle to ADP were greater in the progesterone-treated group than in the progesterone plus estrogen group. These results suggest that progesterone alone minimally affects endothelium-dependent responses. However, progesterone seems to antagonize the stimulatory effects of estrogen on two endothelium-dependent responses that are associated with pertussis toxin-sensitive guanine nucleotide regulatory proteins and the production of nitric oxide. These studies suggest that a specific receptor/second messenger system can be modulated by female reproductive steroid hormones.
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PMID:Progesterone and modulation of endothelium-dependent responses in canine coronary arteries. 168 44

The endothelial cells can release both relaxing and contracting substances. The former include prostacyclin and endothelium-derived relaxing factor (EDRF, which most likely is nitric oxide, or a nitrosoderivative releasing nitric oxide, derived from L-arginine). Candidates as endothelium-derived contracting factors (EDCF) include superoxide anions thromboxane A2 and the peptide endothelin. Endothelium-derived relaxing factor causes relaxation of vascular smooth muscle by activation of the soluble form of guanylate cyclase which leads to an accumulation of cyclic GMP; it also reduces platelet adhesion and aggregation. The latter effect is synergistic with the inhibition evoked by prostacyclin. The release of EDRF and prostacyclin plays a key role in the protective role of the endothelium against vasospasm and the unwanted coagulation of blood. Indeed, thrombin and aggregating platelets are potent stimuli for the release of EDRF. The platelet-products responsible are the adenine nucleotides, ADP and ATP, which activate P2y-purinergic receptors on the endothelial cells and 5-hydroxytryptamine (serotonin) that stimulates 5-HT1-like serotonergic receptors. The response to serotonin, but not that to the adenine nucleotides, is mediated by a pertussis toxin-sensitive mechanism. When endothelial cells regenerate, or are cultured, they selectively lose the pertussis toxin-sensitive mechanism of release, which results in a marked decrease in sensitivity to exogenous and platelet-released serotonin. As a consequence, the endothelial cells exhibit a considerably reduced response to aggregating platelets. This phenomenon, which can be exacerbated by hypercholesterolemia, favors ongoing platelet aggregation and vasospasm, and constitutes a first step toward atherosclerosis.
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PMID:Platelet-derived serotonin, the endothelium, and cardiovascular disease. 171 75

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

A pertussis toxin-sensitive guanine nucleotide regulatory protein (G-protein) is involved in the signal transduction of certain endothelium-dependent responses in mammalian arteries. To determine whether a similar mechanism mediates endothelium-dependent responses in mammalian veins, rings of canine femoral arteries and veins with and without endothelium were suspended for the measurement of isometric force in organ chambers. In femoral arteries, incubation of the rings with pertussis toxin (from Bordetella pertussis, 100 ng/ml for 2 hr) in the presence of indomethacin and propranolol did not reduce significantly endothelium-dependent relaxations to acetylcholine and adenosine diphosphate, thrombin or the calcium ionophore A23187. However, endothelium-dependent relaxations evoked by the alpha-2 adrenergic agonist UK 14,304 were blocked by the pertussis toxin. In venous rings, endothelium-dependent relaxations to acetylcholine were reduced by the toxin, whereas the endothelium-dependent relaxations evoked by adenosine diphosphate, thrombin and A23187 were not affected. UK 14,304 contracted the veins; these contractions were augmented by removal of the endothelium. Pertussis toxin inhibited contractions to UK 14,304 in venous rings without but not with endothelium. Relaxations of arterial and venous smooth muscle to nitric oxide were unaffected by the toxin. Contractions to phenylephrine were not altered by either removal of the endothelium or the toxin in the arteries or veins. These results suggest that the release of endothelium-derived relaxing factor in response to stimulation of purine and thrombin receptors probably does not involve a pertussis toxin-sensitive G-protein in canine femoral arteries or veins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pertussis toxin reduces endothelium-dependent and independent responses to alpha-2- adrenergic stimulation in systemic canine arteries and veins. 185 Apr 67

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

Endothelial cells release nitric oxide from L-arginine, and this pathway can be inhibited by the analogue of L-arginine, NG-monomethyl-L-arginine (L-NMMA). The effect of L-NMMA on endothelium-dependent relaxation of epicardial porcine coronary arteries was studied in isolated blood vessels suspended in organ chambers for isometric tension recording. Endothelium-dependent relaxations to bradykinin, serotonin, and the alpha 2-adrenergic agonist clonidine were evaluated in the presence and absence of L-NMMA (10(-5)-10(-3) M). L-NMMA, as well as the inhibitor of guanylate cyclase methylene blue (10(-5) M) and hemoglobin (10(-5) M), inhibited endothelium-dependent relaxation to serotonin and clonidine. The effect of L-NMMA could be reversed by L-arginine but not by D-arginine. In contrast, L-NMMA, methylene blue, and hemoglobin caused a weak inhibition of the endothelium-dependent relaxation evoked by bradykinin; indomethacin and tranylcypromine had no effect. The inhibitor of Gi proteins pertussis toxin (100 ng/ml) abolished the relaxations evoked by clonidine and markedly reduced those evoked by serotonin but did not affect those caused by bradykinin. In the presence of pertussis toxin, L-NMMA induced a further reduction of the relaxations to serotonin, suggesting that inhibition of Gi proteins does not completely prevent the activation of the L-arginine pathway. Thus endothelium-dependent relaxations to serotonin and to the alpha 2-adrenergic agonist clonidine are mediated through the release of nitric oxide formed from L-arginine in endothelial cells, whereas bradykinin evokes endothelium-dependent relaxations via a different pathway.
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PMID:Different activation of L-arginine pathway by bradykinin, serotonin, and clonidine in coronary arteries. 212 44


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