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)

1. The effects of the selective thromboxane A2 (TXA2) receptor agonist I-BOP on neuronal excitability and synaptic transmission were studied in the CAl neurones of rat hippocampal slices by an intracellular recording technique. 2. Superfusion of I-BOP (0.5 microM) resulted in a biphasic change of the excitatory postsynaptic potential (e.p.s.p.), which was blocked by pretreatment with SQ 29548, a specific antagonist of TXA2 receptors. The inhibitory phase of I-BOP on the e.p.s.p. was accompanied by a decrease in neuronal membrane input resistance. 3. The sensitivity of postsynaptic neurones to glutamate receptor agonists, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) or N-methyl-D-aspartate (NMDA), was unchanged by I-BOP (0.5 microM) pretreatment. 4. Bath application of Ba2+ (0.5 mM) prevented both the I-BOP-induced reduction of the neuronal membrane input resistance and the blockade of e.p.s.p. induced by I-BOP. 5. Intracellular dialysis of the hippocampal CA1 neurones with GDP (10 mM) significantly attenuated the I-BOP inhibition of e.p.s.p. and membrane input resistance. Incubation of the slices with either pertussis toxin (PTX, 5 micrograms ml-1 for 12 h) or cholera toxin (CTX, 5 micrograms ml-1 for 12 h) did not affect the biphasic action of I-BOP on the e.p.s.p. or the reduction of membrane input resistance induced by I-BOP. 6. Pretreatment of the slices with the protein kinase C (PKC) inhibitor, NPC-15437 (20 microM), abolished the biphasic modulation by I-BOP (0.5 microM) of the e.p.s.p. Intracellular application of a specific PKC inhibitor, PKCI 19-36 (20 microM), completely inhibited the I-BOP reduction of e.p.s.p. The specific cyclic AMP-dependent protein kinase (PKA) inhibitor, Rp-cyclic adenosine 3',5'-monophosphate (Rp-cyclic AMPS, 25 microM), had no effect on the I-BOP action. 7. In this study we have demonstrated, for the first time, the existence of functional TXA2 receptors in the hippocampus which mediate the effects of a TXA2 agonist on neuronal excitability and synaptic transmission. Activation of the presynaptic TXA2 receptors may stimulate the release of glutamate. Conversely, activation of postsynaptic TXA2 receptors leads to inhibition of synaptic transmission resulting from a decrease in the membrane input resistance of the neurones. The pre- and postsynaptic actions of the TXA2 agonist are both mediated by PTX- and CTX-insensitive G-protein-coupled activation of PKC pathways.
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PMID:Thromboxane A2 agonist modulation of excitatory synaptic transmission in the rat hippocampal slice. 886 65

The present study evaluates the influence of cholera toxin and its B-subunit on thermic responses to morphine in the rats. The holotoxin (1 microg/rat) and the B-subunit (5 microg) were administered ICV and three days later rats were challenged ICV with morphine and tested for changes of body temperature. Cholera toxin, but not its B-subunit, modified the time course of the hyperthermic response induced by a low dose of morphine (2.5 microg), converted the hypothermia due to a higher dose of morphine (18 microg) to a consistent hyperthermia and only partially reduced the greater hypothermia induced by 36 microg of morphine. Cholera toxin-induced modifications of thermic responses to morphine were paralleled with a decreased Gs(alpha) immunoreactivity and a reduced ability for the toxin to catalyse the "in vitro" ADP-ribosylation of Gs(alpha) in hypothalamic membranes. In contrast, at the same time when morphine-induced effects on body temperature were assessed, no changes in pertussis toxin-mediated ADP-ribosylation of Gi(alpha)/Go(alpha), or basal adenylate cyclase activity, or binding of mu-opioid receptor selective ligand [3H]-DAMGO were observed in hypothalamic areas from rats treated with cholera toxin. These findings suggest that adaptative events secondary to prolonged activation of Gs(alpha) play a role in the modifications of thermic responses to morphine induced by CTX.
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PMID:Cholera toxin effects on body temperature changes induced by morphine. 907 89

1. The cold (4 degrees C) water swimming stress (CWSS) for 3 min significantly increased the inhibition of the tail-flick response in ICR mice. 2. Pertussis toxin (PTX, 0.05-0.5 microgram) in mice pretreated intrathecally (IT) for 6 days attenuated the inhibition of the tail-flick response induced by CWSS. However, intracerebroventricular (ICV) pretreatment with PTX at the same doses did not affect CWSS-induced inhibition of the tail-flick inhibition. 3. 3-Isobutyl-1-methylxanthine (IBMX, 0.01-1 ng) in mice pretreated IT for 10 min dose-dependently attenuated the inhibition of the tail-flick response induced by CWSS. However, IBMX in mice ICV pretreated ICV at the same doses was not effective in attenuating the CWSS-induced inhibition of the tail-flick response. 4. Neither IT nor ICV pretreatment with cholera toxin (CTX, 0.05-0.5 microgram) for 24 hr affected the inhibition of the tail-flick response induced by CWSS. 5. The ICV or IT injection of PTX, CTX, or IBMX did not affect the basal tail-flick response latency. 6. It is concluded that spinal, but not supraspinal, PTX-sensitive G-proteins and cAMP phosphodiesterase may be involved in the antinociception produced by CWSS. However, neither spinal nor supraspinal CTX-sensitive G-proteins appear to be involved in mediating the antinociception induced by CWSS.
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PMID:Effects of spinally and supraspinally injected 3-isobutyl-1-methylxanthine, cholera toxin, and pertussis toxin on cold water swimming stress-induced antinociception in the mouse. 914 32

Whole-cell patch-clamp recordings were used to study Ba2+ currents through voltage-dependent Ca2+ channels in dorsal root ganglion x mouse neuroblastoma hybrid (F-11) cells. Opioid agonists selective for either mu (Tyr-D-Ala-Gly-Mephe-Gly-ol; DAMGO) or delta (Tyr-D-Pen-Gly-Phe-D-Pen-OH; DPDPE) receptors inhibited high-threshold Ba2+ currents. The inhibition was reversible, naloxone-sensitive, and dose-dependent. The inhibitory effects of both DAMGO and DPDPE were blocked by pretreatment of the cells with pertussis toxin (PTX) as well as by brief exposure to the sulfhydryl alkylating agent, N-ethylmaleimide (NEM). The N-type Ca2+ channel antagonist omega-conotoxin GVIA (omega-CTX GVIA) irreversibly inhibited high threshold Ba2+ currents by 66% and blocked the inhibitory effect of DAMGO or DPDPE. In contrast, the L-type Ca2+ channel blocker nifedipine inhibited high threshold Ba2+ currents by 15% and failed to block the inhibitory effect of DAMGO or DPDPE. These results demonstrate that mu and delta opioid receptors are negatively coupled to N-type Ca2+ channels via PTX- and NEM-sensitive GTP-binding proteins in F-11 cells.
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PMID:Mu and delta opioids but not kappa opioid inhibit voltage-activated Ba2+ currents in neuronal F-11 cell. 935 88

In transfected Chinese hamster ovary (CHO-A1) cells the human adenosine A1 receptor directly stimulates pertussis toxin-sensitive increases in inositol phosphate production and potentiates (synergistically) the inositol phosphate responses mediated by Gq-coupled P2Y2 purinoceptor and CCK(A) receptors. In the present study we have investigated the role of Gbetagamma subunits in mediating adenosine A1 receptor effects on phospholipase C activation (both direct and synergistic) by transiently transfecting CHO-A1 cells with a scavenger of Gbetagamma subunits: the C-terminus of beta-adrenoceptor kinase 1 (beta ark1 residues 495-689). [3H]inositol phosphate responses to the selective adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA; 1 microM) were inhibited (41 +/- 1%) in CHO-A1 cells transiently transfected with the Gbetagamma scavenger, beta ark1 (495-689). Expression of beta ark1 (495-689) protein was confirmed by Western blotting. In contrast, adenosine A1 receptor-mediated inhibition of forskolin stimulated [3H]cyclic AMP accumulation was unaffected by transient expression of beta ark1 (495-689). Beta ark1 (495-689) expression had no significant effect on the [3H]inositol phosphate responses produced by activation of the endogenous P2Y2 purinoceptor (100 microM UTP; 92 +/- 0.8% of control). [3H]inositol phosphate accumulation in response to adenosine A receptor activation was also attenuated in CHO-K1 cells co-transfected with the beta ark1 (495-689) minigene (59 +/- 4% inhibition of control response to 1 microM CPA). Finally, transient expression of beta ark1 (495-689) in CHO-A1 cells inhibited the augmentation of [3H]inositol phosphate responses resulting from co-activation of adenosine A1 receptors and P2Y2 purinoceptors. These experiments indicate that Gbetagamma subunits are involved in the direct coupling the adenosine A1 receptor to phospholipase C and that they also participate in the augmentation of P2Y2 purinoceptor-mediated [3H]inositol phosphate responses by the adenosine A1 receptor.
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PMID:Involvement of G-protein betagamma subunits in coupling the adenosine A1 receptor to phospholipase C in transfected CHO cells. 975 42

We investigated the effects of R(-)-1-(benzo[b]thiophen-5-yl)-2-[2-(N,N-diethylamino)ethoxy]ethan ol hydrochloride (T-588), a novel cognitive enhancer, on trimeric GTP-binding proteins (G proteins) and cyclic AMP accumulation in rat cerebral cortex. T-588 (0.1-1.0 mM) inhibited the ADP-ribosylation of alpha subunit of Gs in a concentration-dependent manner. Auto-ADP-ribosylation of CTX was not inhibited by T-588. The stimulatory effect of guanosine 5'-(3-O-thio)triphosphate (GTPgammaS) on CTX-catalyzed ADP-ribosylation was attenuated by adding T-588 in assay mixture. ADP-ribosylation of Gi/Go by pertussis toxin was slightly inhibited by T-588. Isoproterenol-stimulated cyclic AMP accumulation was inhibited by adding 3 mM T-588 to rat cerebral cortical slices. Next, we investigated the effects of isoproterenol and T-588 on GTPgammaS binding. Membranes were first incubated with or without isoproterenol and T-588 in the presence of 0.2mM GTPgammaS, then cholate extract preparations were prepared from the washed membranes. Interestingly, the [32P]ADP-ribosylation of G(s alpha) was enhanced not only by isoproterenol but also by T-588. Although the obtained results are apparently inconsistent, T-588 seems to interact with G proteins, specifically Gs.
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PMID:Effects of T-588, a novel cognitive enhancer, on ADP-ribosylation of G(s alpha) by cholera toxin and cyclic AMP accumulation in rat cerebral cortex. 1021 74

Brain macroglia are known to express a diverse array of neurotransmitter receptors whose signal transduction pathways may be subject to heteroreceptor 'cross-talk'. In the current study we have examined group 1 mGlu receptor-evoked [Ca2+]i signalling, and possible heteroreceptor cross-talk, in cultured type 2 astrocytes. The selective group 1 metabotropic glutamate (mGlu) receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG) elevated [Ca2+]i (EC50 = 1.7 +/- 0.6 microM); an effect reversed by the selective mGlu receptor antagonist (S)-alpha-methyl-4-carboxyphenylglycine (IC50 = 52.7 +/- 8.7 microM). DHPG-evoked [Ca2+]i responses were abolished by (1) thapsigargin (100 nM), implicating the involvement of internal Ca2+ stores in group 1 mGlu [Ca2+]i responses and (2) the removal of extracellular Ca2+. When applied alone, the selective adenosine A1 receptor agonist, N6-cyclopentyladenosine (CPA, 100 nM) failed to influence [Ca2+]i. However, in the presence of 1 microM DHPG, CPA potently (EC50 = 12.3 +/- 1.9 nM) increased [Ca2+]i responses. In the presence of 100 nM CPA, the efficacy of DHPG was doubled without any significant change in the DHPG EC50 value. This effect was reversed by either the selective adenosine A1 receptor antagonist, 8-cyclopentyltheophylline (IC50 = 50.3 +/- 19.9 nM) or overnight incubation with Pertussis toxin (100 ng/ml). We conclude that (1) type 2 astrocytes contain group 1 mGlu receptors coupled to [Ca2+]i signalling and (2) co-activation of adenosine A1 receptors enhances group 1 mGlu-evoked [Ca2+]i responses in these cells via a Gi/o G protein-mediated mechanism.
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PMID:Group 1 mGlu receptors elevate [Ca2+]i in rat cultured cortical type 2 astrocytes: [Ca2+]i synergy with adenosine A1 receptors. 1053 Aug 13

Both beta- and alpha(1)-adrenoceptors mediate the myocardial effects of catecholamines. It is well known that adenosine inhibits beta-dependent effects; however, whether alpha(1)-dependent responses can be similarly modulated is unclear. Accordingly, rat ventricular myocytes were exposed for 25 min to the alpha(1) agonist phenylephrine (2 microM, in the presence of 1 microM propranolol) in the absence or presence of adenosine (100 microM) or the A(1) receptor-selective agonist N(6)-cyclopentyladenosine (CPA, 1 microM). We also investigated the effects of K(ATP) blockade with glibenclamide (1 microM), the protein kinase C inhibitor bisindolylmaleimide (20 nM), and pertussis toxin (300 ng/ml), which uncouples G(i) protein/receptor interaction, and assessed whether effects of adenosine were mimicked by K(ATP) activation with either pinacidil or cromakalim (5 microM). Phenylephrine significantly increased cell shortening by 190% and the Ca(2+) transient by 24%, which was abolished by either adenosine or CPA, but not in the presence of the A(1) receptor-selective antagonist 8-cyclopentyl-1, 3-dipropylxanthine (1 microM), and was abolished by pertussis toxin. The effect of adenosine or CPA was reversed by glibenclamide and mimicked by either cromakalim or pinacidil. Bisindolylmaleimide was without effect. The A(2) or A(3) receptor agonists 2-(4-(2-carboxyethyl)phenylethylamino)-5'-N-ethylcarboxamidoade nos ine and N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (1 microM each), respectively, were without effect. Neither CPA nor adenosine modulated the effect of endothelin-1 (5 nM), which also acts via the phosphoinositide hydrolysis pathway. We conclude that adenosine selectively inhibits alpha(1)-adrenergic-mediated effects in rat ventricular myocytes through a G(i) protein-dependent mechanism involving A(1) receptor and K(ATP) activation. Our study further suggests that endogenous adenosine may modulate alpha(1)-mediated effects of catecholamines.
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PMID:Inhibition of alpha(1)-adrenergic-mediated responses in rat ventricular myocytes by adenosine A(1) receptor activation: role of the K(ATP) channel. 1090 Feb 59

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


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