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)

In prior studies, we showed that cholera (CTX) and pertussis toxins (PTX) increase rat liver endosome acidification. This study was performed to characterize the effects of these toxins and cyclic adenosine monophosphate (cAMP) on endosome ion transport, fluid-phase endocytosis (FPE), and endosome trafficking in liver. In control liver, more mature populations of endosomes acidified progressively more slowly, but both toxins and cAMP caused retention of an early endosome acidification profile in maturing endosomes. CTX caused a density shift in endosomes, and all agents increased net FPE at time points from 5 to 60 minutes. By confocal microscopy, fluorescent dextrans first appeared in small vesicles at the hepatocyte sinusoidal membrane and trafficked rapidly to the pericanalicular area, near lysosomes and the trans-Golgi network (TGN). Prolonged exposure to these agents caused redistribution of many labeled vesicles to the perinuclear region, colocalized with markers of both early (EEA1 and transferrin receptor) and late (LAMP1) endosomes. We conclude that cAMP is the common agent that disrupted normal maturation and trafficking of endosomes and increased net FPE, in part via decreased diacytosis.
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PMID:Effect of cholera toxin and cyclic adenosine monophosphate on fluid-phase endocytosis, distribution, and trafficking of endosomes in rat liver. 1109 43

In mice pretreated intracerebroventricularly (i.c.v.) with pertussis or cholera toxins, effects of neuropeptide FF (NPFF), on hypothermia and morphine-induced analgesia, were assessed. NPFF and a potent NPFF agonist, 1DMe (0.005-22 nmol) injected into the lateral ventricle decreased morphine analgesia and produced naloxone (2.5 mg x kg(-1), s.c.)-resistant hypothermia after administration into the third ventricle. Cholera toxin (CTX 1 microg, i.c.v.) pretreatment (24 or 96 h before) inhibited the effect of 1DMe on body temperature, but failed to reverse its anti-opioid activity in the tail-flick test. CTX reduced hypothermia induced by a high dose of morphine (8 nmol, i.c.v.) but not the analgesic effect due to 3 nmol morphine. Pertussis toxin (PTX) pretreatment inhibited both morphine-hypothermia and -analgesia but did not modify hypothermia induced by 1DMe. The present results suggest that NPFF-induced hypothermia depends on the stimulation of Gs (but not Gi) proteins. In contrast, anti-opioid effects resulting from NPFF-receptor stimulation do not involve a cholera toxin-sensitive transducer protein.
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PMID:Cholera and pertussis toxins inhibit differently hypothermic and anti-opioid effects of neuropeptide FF. 1117 73

In rat astrocytes, incubation with cholera toxin (CTX; 0.1 microg/ml) for 8 h increased proenkephalin (proENK) mRNA level (10-fold), which was further increased by dexamethasone (DEX; 1 microM) (2.2-fold as much as CTX alone). Although pertussis toxin (PTX; 0.1 microg/ml) did not affect the basal proENK mRNA level, DEX significantly increased proENK mRNA level in PTX-treated cells (6-fold). The inhibition of protein synthesis by cycloheximide (CHX; 15 microM) also increased proENK mRNA level in PTX-treated cells (5.2-fold), but not in CTX-stimulated cells. The treatment with CTX, but not PTX, increased c-Fos and Fra-2 protein levels as well as AP-1, CRE, or ENKCRE-2 DNA binding activity, but neither toxin affected Fra-1, c-Jun, JunB, and JunD protein levels. CHX significantly attenuated CTX-induced increase of c-Fos or Fra-2 protein level and AP-1, CRE, or ENKCRE-2 DNA binding activity, although CHX alone did not affect the basal AP-1, CRE, and ENKCRE-2 DNA binding activities. Phosphorylated CREB level was increased by both CTX and PTX, although the magnitude of phosphorylation of CREB by PTX was much less than that by CTX. In addition, CHX further or persistently increased PTX- or CTX-induced phosphorylated CREB levels in parallel with increases in proENK mRNA. However, DEX did not alter the basal or stimulated phosphorylated-CREB level. These results suggest that the elevation of phosphorylation of CREB rather than AP-1 level may be involved in CTX-induced and CHX-dependent-PTX-induced increase of proENK mRNA level. In addition, AP-1 expression or CREB phosphorylation appears not to be involved the potentiative action of DEX on proENK mRNA expression in CTX- and PTX-treated astrocytes.
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PMID:The comparative analysis of proenkephalin mRNA expression induced by cholera toxin and pertussis toxin in primary cultured rat cortical astrocytes. 1129 34

Because insulin resistance/diabetes may cause inordinate vascular complications in females, we have investigated the effects of insulin and insulin-like growth factor (IGF-1) on vascular reactivity in 12-week-old female Zucker obese (Ob) rats, a rodent model of insulin resistance and its lean (Ln) age-matched counterpart. Endothelium intact aortic rings from Ob animals and their Ln littermates (12 weeks of age) were subjected to contractile concentration responses to phenylephrine (PE) followed by relaxation to isoproterenol (Iso), with and without preincubation for 2 hours with cholera toxin (CTX; 1 microg/mL) or pertussis toxin (PTX; 2 microg/mL) and before and after incubation with either insulin or IGF-1 (100 nmol/L) for 1 hour. Systolic blood pressure was higher (138 +/- 3 v. 109 +/- 4 mm Hg; P <.0001) in the 12-week-old Ob rats. Contractile responses to PE were similar in both groups; however, both insulin and IGF-1 induced a paradoxical increase (P <.001) in contraction in Ob vasculature (929 +/- 92 v. 679 +/- 25 mg, respectively). CTX alone decreased contraction in the Ob (P <.02) and PTX in the Ln (P <.02), but there were no interactions between either IGF-1 or insulin and the toxins. Marked impairment of relaxation to Iso was seen in aortic rings of these female Ob rats (ED(50) = 2.6 micromol/L v. 418 nmol/L, P =.0002), an effect exacerbated by preincubation with either insulin or IGF-1 (P =.0001). Again, no role for G-proteins could be demonstrated. Insulin-dependent glucose uptake was severely impaired (P <.05) in aortic segments of the Ob insulin-resistant rats. Insulin receptor binding, tyrosine kinase activity (TKA), and abundance of several G-protein alpha subunits (inhibitory and stimulatory) in solubilized arterial membrane preparations (assessed by Western blot) were comparable in the 2 groups. These results indicate that resistance to the vascular actions of insulin/IGF-1 in female Ob rats is a postreceptor event that parallels glucose uptake resistance and is independent of G-proteins.
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PMID:Vascular insulin/insulin-like growth factor-1 resistance in female obese Zucker rats. 1131 26

1. The present study investigates the mechanisms by which polyphenolic compounds from red wine elicit Ca(2+) mobilization in bovine aortic endothelial cells (BAECs). Two polyphenol-containing red wine extracts, red wine polyphenolic compounds (RWPC) and Provinols, and delphinidin, an anthocyanin were used. 2. RWPC stimulated a Ca(2+)-dependent release of nitric oxide (NO) from BAECs accounting for the relaxation of endothelium-denuded rat aortic rings as shown by cascade bioassay. 3. RWPC, Provinols and delphinidin increased cytosolic free calcium ([Ca(2+)](i)), by releasing Ca(2+) from intracellular stores and by increasing Ca(2+) entry. 4. The RWPC-induced increase in [Ca(2+)](i) was decreased by exposure to ryanodine (30 microM), whereas Provinols and delphinidin-induced increases in [Ca(2+)](i) were decreased by bradykinin (0.1 microM) and thapsigargin (1 microM) pre-treatment. 5. RWPC, Provinols and delphinidin-induced increases in [Ca(2+)](i) were sensitive to inhibitors of phospholipase C (neomycin, 3 mM; U73122, 3 microM) and tyrosine kinase (herbimycin A, 1 microM). 6. RWPC, Provinols and delphinidin induced herbimycin A (1 microM)-sensitive tyrosine phosphorylation of several intracellular proteins. 7. Provinols released Ca(2+) via both a cholera (CTX) and pertussis toxins (PTX)-sensitive pathway, whereas delphinidin released Ca(2+) only via a PTX-sensitive mechanism. 8. Our data contribute in defining the mechanisms of endothelial NO production caused by wine polyphenols including the increase in [Ca(2+)](i) and the activation of tyrosine kinases. Furthermore, RWPC, Provinols and delphinidin display differences in the process leading to [Ca(2+)](i) increases in endothelial cells illustrating multiple cellular targets of natural dietary polyphenolic compounds.
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PMID:Red wine polyphenols increase calcium in bovine aortic endothelial cells: a basis to elucidate signalling pathways leading to nitric oxide production. 1190 73

1. Non-adrenergic non-cholinergic (NANC) relaxant responses were elicited by electrical field stimulation (EFS) in rabbit vaginal wall strips after treatment with guanethidine and scopolamine and raising smooth muscle tone with phenylephrine. Under these conditions treatment with NOS inhibitors revealed a non-nitrergic NANC relaxant response. The possible role of purines and pyrimidines in these non-nitrergic NANC responses was investigated. 2. Exogenous application of ATP, ADP, adenosine, UTP, or UDP (all at 0.03-10 mM) induced concentration-dependent relaxant responses. 3. Responses to exogenous application of ATP were reduced by the general P2 antagonist cibacron blue (500 micro M), but not by suramin (100 micro M) and were unaffected by L-NAME (500 micro M), omega-conotoxin GVIA (omega-CTX, 500 nM) or tetrodotoxin (TTX, 1 micro M). 4. Responses to exogenous application of adenosine were reduced by the A(2A) antagonist ZM-241385 (30 micro M). 5. ATP- and ADP-induced responses were unaffected by the G-protein inhibitor pertussis toxin (100 ng ml(-1)), whilst ADP- but not ATP-induced responses were reduced by GDPbetaS (100 micro M), which stabilizes G-proteins in their inactive state. 6. EFS-induced non-nitrergic NANC relaxant responses were unaffected by suramin, cibacron blue, ZM-241385, pertussis toxin or GDPbetaS, but were completely inhibited by TTX. 7. Exogenous application of ATP (10 mM) and adenosine (10 mM) increased intracellular cyclic adenosine-3', 5'-monophosphate (cAMP). However, non-nitrergic NANC responses were not associated with increased cAMP. Neither non-nitrergic NANC responses nor responses to ATP or adenosine were associated with increased intracellular cyclic guanosine-3', 5'-monophosphate (cGMP) concentrations. 8. These results suggest that adenosine A(2A) receptors and P2 receptors are present in the rabbit vaginal wall, but that they are not involved in non-nitrergic NANC relaxant responses.
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PMID:Purines and pyrimidines are not involved in NANC relaxant responses in the rabbit vaginal wall. 1235 33

We have previously reported that dopamine (DA) depresses non-NMDA receptor-mediated glutamatergic transmission in the rat parabrachial nucleus (PBN), an interface between brainstem and forebrain that is implicated in autonomic regulation. This work examined cellular signalling pathways that might underlie this DA-induced synaptic depression. Direct activation of adenylyl cyclase with 10 microM forskolin increased the evoked EPSC but did not occlude DA-induced EPSC depression. Similarly, a preferential protein kinase A inhibitor, H-7 (10 microM), did not block DA's synaptic effects. Incubation of slices with cholera toxin (CTX; 1 microgram/ml) or pertussis toxin (PTX; 0.5 microgram/ml) for 20 h, procedures used to irreversibly activate or disable the G(s) and G(i) proteins, respectively, did not change DA's effects. The putative phospholipase C inhibitor, U-73122 (10 microM) and its inactive analogue U-73343 (10 microM) did not alter DA-induced reduction in the EPSCs. Alterations in signalling molecules downstream of phospholipase C including depleting internal calcium stores by thapsigargin and cyclopiazonic acid and blocking protein kinase C with chelerythrine, had no effect on DA-induced synaptic depression. Furthermore, DA's depression of the non-NMDA response was not blocked by APV, an NMDA receptor antagonist. Finally, DA depressed evoked, pharmacologically isolated NMDA receptor-mediated synaptic responses while increasing NMDA-induced inward currents in the PBN. These results indicate that DA-induced synaptic effects in the PBN are not through the activation of cholera or pertussis toxin sensitive G proteins. Furthermore, it does not employ the adenylyl cyclase-cAMP-PKA cascade, the phospholipase C signalling pathway and NMDA receptor-coupled mechanisms to depress excitatory synaptic transmission in the PBN.
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PMID:Dopamine-induced synaptic depression in the parabrachial nucleus is independent of CTX- and PTX-sensitive G-proteins, PKA and PLC signalling pathways. 1467 13

This study evaluated the response of the Na(+)/H(+) exchanger (NHE) to dopamine D(1)- and D(2)-like receptor stimulation in immortalized renal proximal tubular epithelial cells and freshly isolated renal proximal tubules from the spontaneously hypertensive rat (SHR) and their normotensive controls (Wistar Kyoto rats; WKY). Stimulation of D(1)-like receptors with SKF 38393 attenuated NHE activity in WKY cells (IC(50)=151 nM), but not in SHR cells. Stimulation of D(2)-like receptors with quinerolane (IC(50)=120 nM) attenuated NHE activity in SHR cells, but not in WKY cells. Forskolin was equipotent in SHR and WKY cells in inhibiting NHE activity. The effect of SKF 38393 was abolished by overnight treatment of WKY cells with cholera toxin (CTX, 500 ng ml(-1)), but not with pertussis toxin (PTX, 100 ng ml(-1)). The effect of quinerolane (1 microm) was abolished by overnight treatment of SHR cells with PTX, but not with CTX. The D(3) receptor agonist 7-OH-DPAT (IC(50)=0.8 microM) attenuated NHE activity in SHR cells only. This effect was abolished by S-sulpiride and by overnight treatment with PTX. The D(4) receptor agonist RBI 257 did not affect NHE activity. The 7-OH-DPAT inhibited NHE activity in freshly isolated renal proximal tubules from 4- and 12-week-old SHR and 12-week-old WKY, but not in freshly isolated renal proximal tubules from 4-week-old WKY. It is concluded that D(3) receptors coupled to a G(i/o) protein play a role in the handling of tubular Na(+), namely through inhibition of the NHE activity, this being of particular relevance in the SHR, which fail to respond to D(1)-like dopamine receptor stimulation.
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PMID:Dopamine D3 receptor-mediated inhibition of Na+/H+ exchanger activity in normotensive and spontaneously hypertensive rat proximal tubular epithelial cells. 1526 11

NO released by myenteric neurons controls the off contraction induced by electrical field stimulation (EFS) in distal esophageal smooth muscle, but in the presence of nitric oxide synthase (NOS) inhibitor, L-NAME, contraction by EFS occurs at the same time. The authors investigated the intracellular signaling pathways related with G protein and ionic channel EFS-induced contraction using cat esophageal muscles. EFS-induced contractions were significantly suppressed by tetrodotoxin (1 microM) and atropine (1 microM). Furthermore, nimodipine inhibited both on and off contractions by EFS in a concentration dependent meaner. The characteristics of 'on' and 'off' contraction and the effects of G-proteins, phospholipase, and K(+) channel on EFS-induced contraction in smooth muscle were also investigated. Pertussis toxin (PTX, a G(i) inactivator) attenuated both EFS-induced contractions. Cholera toxin (CTX, G(s) inactivator) also decreased the amplitudes of EFS-induced off and on contractions. However, phospholipase inhibitors did not affect these contractions. Pinacidil (a K(+) channel opener) decreased these contractions, and tetraethylammonium (TEA, K(+) (Ca) channel blocker) increased them. These results suggest that EFS-induced on and off contractions can be mediated by the activations Gi or Gs proteins, and that L-type Ca(2+) channel may be activated by G-protein alpha subunits. Furthermore, K(+) (Ca)-channel involve in the depolarization of esophageal smooth muscle. Further studies are required to characterize the physiological regulation of Ca(2+) channel and to investigate the effects of other K(+) channels on EFS-induced on and off contractions.
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PMID:The influences of g proteins, ca, and k channels on electrical field stimulation in cat esophageal smooth muscle. 1991 3

Anti-inflammatory activities of thymoquinone (TQ) have been demonstrated in in vitro and in vivo studies. However, the precise mechanism(s) of TQ in these anti-inflammatory activities is not well understood. Using a newly developed assay to detect sialidase activity in live macrophage cells (Glycoconj J doi: 10.1007/s10719-009-9239-8 ), here we show that TQ has no inhibitory effect on endotoxin lipopolysaccharide (LPS) induced sialidase activity in live BMC-2 macrophage cells. In contrast, the parent black seed oil (BSO) and another constituent of BSO para-cymene (p-CY) completely block LPS induced sialidase activity. All of these compounds had no effect on cell viability. On the other hand, TQ induces a vigorous sialidase activity in live BMC-2 macrophage cells in a dose dependent manner as well in live DC-2.4 dendritic cells, HEK-TLR4/MD2, HEK293, SP1 mammary adenocarcinoma cells, human WT and 1140F01 and WG0544 type I sialidosis fibroblast cells. Tamiflu (oseltamivir phosphate) inhibits TQ-induced sialidase activity in live BMC-2 cells with an IC(50) of 0.0194 microM compared to an IC(50) of 19.1 microM for neuraminidase inhibitor DANA (2-deoxy-2,3-dehydro-N-acetylneuraminic acid). Anti-Neu1, -2 and -3 antibodies have no inhibition of TQ-induced sialidase activity in live BMC-2 and human THP-1 macrophage cells but anti-Neu4 antibodies completely block this activity. There is a vigorous sialidase activity associated with TQ treated live primary bone marrow (BM) macrophage cells derived from WT and hypomorphic cathepsin A mice with a secondary Neu1 deficiency (NeuI KD), but not from Neu4 knockout (Neu4 KO) mice. Pertussis toxin (PTX), a specific inhibitor of Galphai proteins of G-protein coupled receptor (GPCR) and the broad range inhibitors of matrix metalloproteinase (MMP) galardin and piperazine applied to live BMC-2, THP-1 and primary BM macrophage cells completely block TQ-induced sialidase activity. These same inhibitory effects are not observed with the GM1 ganglioside specific cholera toxin subunit B (CTXB) as well as with CTX, tyrosine kinase inhibitor K252a, and the broad range GPCR inhibitor suramin. The specific inhibitor of MMP-9, anti-MMP-9 antibody and anti-Neu4 antibody, but not the specific inhibitor of MMP-3 completely block TQ-induced sialidase activity in live THP-1 cells, which express Neu4 and MMP-9 on the cell surface. Neu4 sialidase activity in cell lysates from TQ-treated live THP-1 cells desialylates natural gangliosides and mucin substrates. RT-PCR and western blot analyses reveal no correlation between mRNA and protein values for Neu3 and Neu4 in human monocytic THP-1 cells, suggesting for the first time a varied post-transcriptional mechanism for these two mammalian sialidases independent of TQ activation. Our findings establish an unprecedented activation of Neu4 sialidase on the cell surface by thymoquinone, which is derived from the nutraceutical black cumin oil. The potentiation of GPCR-signaling by TQ via membrane targeting of Galphai subunit proteins and matrix metalloproteinase-9 activation may be involved in the activation process of Neu4 sialidase on the cell surface.
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PMID:Thymoquinone from nutraceutical black cumin oil activates Neu4 sialidase in live macrophage, dendritic, and normal and type I sialidosis human fibroblast cells via GPCR Galphai proteins and matrix metalloproteinase-9. 2021 45


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