UMLS:C0043167 - FACTA Search

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

In this study, we examined the response of spontaneously active as well as quiescent cells (L-glutamate-activated) in the rat medial prefrontal cortex (mPFc) to the iontophoresis of 2-methylserotonin (2-Me-5-HT, 5-HT3 receptor agonist), (+/-)-2,5-dimethoxy-(4-iodo-phenyl)-2-aminopropane (DOI, 5-HT2A,2C receptor agonist), 8-hydroxy-N,N-di-propylamino tetralin (8-OH-DPAT, 5-HT1A receptor agonist) and gamma-aminobutyric acid (GABA, a non-selective GABA receptor agonist) after the intracerebral administration of pertussis toxin, an inactivator of the Gi/o protein. This was accomplished using the techniques of extracellular single cell recording and iontophoresis. The administration of pertussis toxin (0.5 microgram, 24 hours before the experiment) into the mPFc did not alter the response of mPFc cells to the iontophoresis of DOI, 2-Me-5HT or GABA compared to saline treated controls. However, the response of mPFc cells to the iontophoresis of 8-OH-DPAT was significantly attenuated in the animals pretreated with pertussis toxin compared to controls. These results suggest that the 5-HT1A but not 5-HT2A,2C or 5-HT3 receptor is coupled to the Gi/o protein.
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PMID:Effect of pertussis toxin on the response of rat medial prefrontal cortex cells to the iontophoresis of serotonin receptor agonists. 786 72

Iontophoresis of dopamine or the D1 agonist SKF 38393 has been shown to elicit current-dependent increases in the firing of rat substantia nigra pars reticulata neurons, suggesting a discrete physiological role for the D1 dopamine receptor population in the substantia nigra. The effects of SKF 38393 differed from those of dopamine, however, in that the D1 agonist also augmented inhibitory responses to applied GABA, whereas dopamine and D2-like agonists were previously found to attenuate responses to GABA. The present studies involved various manipulations of the nigral D1 receptors in order to examine the pharmacological specificity, receptor localization, and second messenger coupling underlying the D1 agonist response. The excitatory and GABA-potentiating effects of SKF 38393 were found to be attributable to D1 receptor stimulation, rather than a nonspecific action, since (1) the effect was mimicked by iontophoresis of A-68930, a D1 agonist of a different structural class than SKF 38393, and (2) the response to SKF 38393 was prevented by intranigral injection of the receptor inactivator N-ethoxy-carbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ; 50 nmol/0.5 microliter) 1 d before, or the D1 antagonist SCH 23390 (1 microgram/microliter) 1 hr before electrophysiological testing. Additional studies revealed that the involved D1 receptors were located presynaptically on striatonigral terminals. For instance, in rats given ipsilateral striatal kainic acid lesions 1 week earlier, application of SKF 38393 failed to elicit the usual increases in cell firing, but loss of the response was observed only among the group of pars reticulata neurons that were shown to be unresponsive to striatal stimulation (i.e., those whose striatonigral inputs had been terminated by the lesion). Finally, to examine the second messenger coupling characteristics of the involved D1 receptors, several membrane-permeable analogs of cAMP were tested iontophoretically in place of SKF 38393. Surprisingly, none of these compounds gave a pattern of response typical of the D1 agonist, raising questions about the involvement of cAMP. Even more suggestive of an unconventional D1 coupling pathway, the excitatory and GABA-potentiating effects of applied SKF 38393 were completely abolished by prior intranigral injection of the G(i)/G(o) protein inactivator, pertussis toxin. Collectively, these results suggest that stimulation of D1 receptors on striatonigral terminals causes an excitation of substantia nigra pars reticulata neurons with an exaggerated responsiveness to GABA, and the effects appear to be mediated by a pertussis toxin-sensitive (i.e., a non-G-like) G-protein and possibly a second messenger other than cAMP.
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PMID:D1 agonist-induced excitation of substantia nigra pars reticulata neurons: mediation by D1 receptors on striatonigral terminals via a pertussis toxin-sensitive coupling pathway. 791 24

The present study was undertaken to investigate the nature of the effect of pertussis toxin on the responsiveness of two potentially distinct subgroups of postsynaptic serotonin1A (5-HT1A) receptors of rat hippocampus CA3 pyramidal neurons: those located at the level of the cell body, which can be activated by microiontophoretically-applied 5-HT1A receptor agonists, and those located on dendrites, which can be activated by endogenous serotonin released by the stimulation of the ascending serotoninergic pathway. The former receptors (denoted as extrasynaptic) have been previously demonstrated to be sensitive to pertussis toxin, whereas the latter (denoted as intrasynaptic) have been shown to be pertussis toxin-insensitive. Rats treated with the 5-HT1A receptor agonists flesinoxan or BMY 42568 were used to determine whether tonic activation of extrasynaptic 5-HT1A receptors would prevent their inactivation by pertussis toxin. A pretreatment with p-chlorophenylalanine was used to determine whether a serotonin depletion would render the intrasynaptic 5-HT1A receptors sensitive to pertussis toxin. The responsiveness of CA3 pyramidal neurons to the suppressant effects of microiontophoretically-applied serotonin, 8-hydroxy-2-(di-n-propylamin)-tetralin, baclofen and GABA or to endogenously-released serotonin, elicited by the stimulation of the ascending serotoninergic pathway, was studied one to 10 days after the intrahippocampal injection of pertussis toxin. When compared to control saline-treated rats, the treatments with flesinoxan (5 mg/kg/day, s.c.) and BMY 42568 (5 mg/kg/day, s.c.) delivered for 14 days by osmotic minipumps, starting three days prior to the injection of pertussis toxin, significantly attenuated the effect of pertussis toxin on the responsiveness of CA3 pyramidal neurons to microiontophoretic applications of serotonin and 8-hydroxy-2-(di-n-propylamino)-tetralin, as well as baclofen, an agonist of GABAB receptors, which share the same G proteins with 5-HT1A receptors. The two-day pretreatment with p-chlorophenylalanine (350 mg/kg/day, i.p.) did not render the intrasynaptic 5-HT1A receptors sensitive to pertussis toxin, as indicated by the unchanged efficacy of the stimulation of the ascending serotonin pathway in the suppressing the firing activity of CA3 dorsal hippocampus pyramidal neurons. Our results suggest that the sustained activation of extrasynaptic 5-HT1A receptors prevents the pertussis toxin-induced ADP ribosylation of G protein alpha subunit, and thereby protects an amount of G proteins sufficient to maintain the function, not only of 5-HT1A, but also of GABAB receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Agonist occupation of serotonin1A receptors in the rat hippocampus prevents their inactivation by pertussis toxin. 796 92

Following postsynaptic activation of a pyramidal cell, the degree of GABAergic synaptic inhibition that the cell receives is reduced dramatically for many seconds. Previously, we found that induction of depolarization-induced suppression of inhibition (DSI) required post-synaptic increases in intracellular [Ca2+], but absence of a decrease in responsiveness to iontophoretically applied GABA left the mechanism of DSI expression uncertain. We investigated DSI with whole-cell voltage-clamp recordings in rat hippocampal slices. Bath-applied carbachol was ordinarily used to increase the spontaneous action potential-induced IPSCs (sIPSCs) and enhance detectability of DSI; synaptically released ACh has the same effects. TTX-sensitive sIPSCs are markedly reduced by DSI, whereas TTX-insensitive miniature IPSC amplitudes do not change, suggesting that DSI represents a retrograde influence on presynaptic GABA release. A lag (approximately 1 s) prior to maximal DSI and prevention of DSI by pertussis toxin pointed to a G protein-linked second messenger that may be presynaptic, since perturbation of postsynaptic G protein function did not alter DSI.
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PMID:Depolarization-induced suppression of GABAergic inhibition in rat hippocampal pyramidal cells: G protein involvement in a presynaptic mechanism. 799 36

1. The electrophysiological action of the mu-opioid receptor-preferring agonist D-Ala2, MePhe4, Met(O)5-ol-enkephalin (FK 33-824) on synaptic transmission has been studied in area CA3 of organotypic rat hippocampal slice cultures. 2. FK 33-824 (1 microM) had no effect on the amplitude of pharmacologically isolated N-methyl-D-aspartate (NMDA) or non-NMDA receptor-mediated EPSPs. 3. FK 33-824 (10 nM to 10 microM) reduced the amplitude of monosynaptic inhibitory postsynaptic potentials (IPSPs) that were elicited in pyramidal cells with local stimulation after pharmacological blockade of excitatory amino acid receptors. This effect was reversible, dose-dependent, and sensitive to naloxone and the mu-receptor antagonist Cys2,Tyr3,Orn5,Pen7-amide (CTOP). FK 33-824 at 1 microM caused a mean reduction in the amplitude of the monosynaptic IPSP of 70%. 4. Neither delta- nor kappa-receptor-preferring agonists had any effect on excitatory or inhibitory synaptic potentials. 5. The disinhibitory action of FK 33-824 was blocked by incubating the cultures with pertussis toxin (500 ng/ml for 48 h) or by stimulation of protein kinase C with phorbol 12,13-dibutyrate (PDBu, 0.5 microM). 6. The depression of monosynaptic IPSPs by FK 33-824 was unaffected by extracellular application of the K+ channel blockers Ba2+ or Cs+ (1 mM each). 7. FK 33-824 produced a decrease in the frequency of miniature, action potential-independent, spontaneous inhibitory synaptic currents (mIPSCs) recorded with whole-cell voltage-clamp techniques, but did not change their mean amplitude. Application of the Ca2+ channel blocker Cd2+ (100 microM) or of nominally Ca(2+)-free solutions did not alter either the frequency and amplitude of mIPSCs or the reduction of mIPSC frequency induced by FK 33-824. 8. The effect of FK 33-824 on spontaneous mIPSCs was prevented by naloxone, and by incubation of cultures with pertussis toxin. 9. These results indicate that mu-opioid receptors decrease GABA release presynaptically by a G protein-mediated inhibition of the vesicular GABA release process, and not by changes in axon terminal K+ or Ca2+ conductances that are sensitive to extracellular Ba2+, Cs+ or Cd2+.
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PMID:Mechanism of mu-opioid receptor-mediated presynaptic inhibition in the rat hippocampus in vitro. 830 42

In contrast to its inhibitory role in mature neurons, GABA can exert excitatory actions in developing neurons, including mediation of increases in cytosolic Ca2+. Modulation of this excitatory activity has not been studied previously. We used Ca2+ digital imaging with Fura-2 to test the hypothesis that neuropeptide Y (NPY) would depress GABA-mediated Ca2+ rises in neurons cultured from the developing suprachiasmatic nucleus (SCN). SCN neurons were chosen as a model system for this study because SCN neurons are primarily GABAergic, they express high levels of NPY and GABA receptors, and functionally, NPY causes profound phase-shifts in SCN-generated circadian rhythms. Vigorous GABA-mediated Ca2+ activity was found in young SCN neurons that were maintained in vitro for 4-14 d. NPY showed a dose-dependent rapid depression of the amplitude of Ca2+ rises generated by GABA released from presynaptic SCN axons. NPY exerted a long-term depression of cytosolic CA2+ in the majority of neurons tested, which lasted more than 1 hr after NPY washout. The magnitude of the NPY depression was dose-dependent. NPY did not affect Ca2+ levels when GABAA receptor activity was blocked by bicuculline; however, when bicuculline and NPY were withdrawn from the perfusion solution, the subsequent CA2+ rise was either significantly reduced or completely absent, suggesting that the NPY receptor was activated in the absence of elevated intracellular Ca2+ and GABAA receptor activity, and that the latent effect of NPY was revealed only after depolarizing GABA stimulation was renewed. Pretreating neurons with pertussis toxin greatly reduced the ability of NPY to depress GABAergic Ca2+ rises, suggesting that the NPY modulation of the GABA activity was based largely on a mechanism involving pertussis toxin-sensitive Gi/Go proteins. NPY receptor stimulation depressed (< 30%) postsynaptic Ca2+ rises evoked by GABA (20 microM) application in the presence of tetrodotoxin (TTX). The effects of NPY were mimicked by the NPY Y1 receptor agonist [Pro34,Leu31] NPY and the Y2 receptor agonist NPY 13-36 and by peptide YY (PYY). Together, our data suggest that the Y1 and Y2 type NPY receptors act both presynaptically and postsynaptically to depress GABA-mediated Ca2+ rises. If related mechanisms exist in peptide modulation of inhibitory GABA activity in mature neurons, this could underlie long-term changes in the behavior of neurons of the SCN necessary for phase-shifting the circadian clock by NPY, NPY also modulated GABA responses in neuroendocrine neurons from the hypothalamic arcuate nucleus. NPY thus can play an important role in evoking long-term depression of GABA-mediated Ca2+ activity in these developing neurons, allowing NPY-secreting cells to modulate the effects of GABA on neurite outgrowth, gene expression, and physiological stimulation. This is the first example of such a cellular memory: that is, long-term Ca2+ depression based on modulation of depolarizing GABA activity.
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PMID:Neuropeptide Y depresses GABA-mediated calcium transients in developing suprachiasmatic nucleus neurons: a novel form of calcium long-term depression. 862 85

The effects of serotonin (5-HT) and GABA on two Ca2+ currents, a transient low-voltage-activated current (tLVA) and a sustained high-voltage-activated current (sHVA) were examined in isolated photoreceptors of Hermissenda. The sHVA current was blocked by 5-HT and reduced by activation of protein kinase C (PKC) with phorbol 12-myristate 13-acetate. The effects of 5-HT were transiently reversed by staurosporine and partially blocked by the PKC inhibitor peptide [PKC(19-36)]. GABA enhanced both the tLVA and sHVA currents at low concentrations (5 nM to 5 microM) and reduced the sHVA current at high concentrations (>10 microM). The GABA-mediated enhancement of the Ca2+ current at low concentrations was sensitive to block by picrotoxin. The protein kinase A (PKA) inhibitor peptide [PKI(6-22)amide] blocked enhancement of both Ca2+ currents produced by cAMP analogs and GABA, suggesting that the effects at low concentrations may be PKA mediated. Caged GTP-gamma-S released by flash photolysis reduced the sHVA current, and pretreatment of the photoreceptors with pertussis toxin blocked the effects of higher concentrations of GABA, indicating that at higher concentrations, the effects may be G-protein mediated.
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PMID:Protein kinase and G-protein regulation of Ca2+ currents in Hermissenda photoreceptors by 5-HT and GABA. 876 66

Whole-cell patch-clamp recordings were performed to study ionic and molecular mechanisms by which cholecystokinin (CCK) peptides modulate the membrane excitability of acutely dissociated rat neostriatal neurons. Immunohistochemical staining studies indicated that about 95% of acutely isolated neostriatal neurons were GABA(gamma-aminobutyric acid)ergic medium-sized cells. During current-clamp recordings, sulfated cholecystokinin octapeptide (CCK-8) depolarized neostriatal neurons and evoked action potentials. During voltage-clamp recordings, CCK-8 induced inward currents at negative membrane potentials by increasing the voltage-insensitive and non-selective cationic conductance. Cholecystokinin tetrapeptide (CCK-4), a selective CCKB receptor agonist, also evoked cationic currents. The CCK-8-induced cation currents were antagonized by PD135,158 (4-{[2-[[3-(1H-indol-3yl)-2-mehtyl-1-oxo-2-[[[1.7.7.-trimeth yl-bicyclo [2.2.1]hept-2-yl)oxy]carbonyl]amino]propyl]amino]-1-phenylethyl]amino-4- oxo- [1S-1 alpha, 2 beta [S*(S*)]4 alpha]}-butanoate N-methyl-D-glucamine), a highly specific and potent CCKB receptor antagonist. The CCK-8-evoked inward currents were blocked by the internal perfusion of 1 mM GDP-beta-S. In neostriatal neurons dialyzed with 0.5 mM GTP-gamma-S, the cationic currents produced by CCK-8 became irreversible. Pretreating neostriatal neurons with 500 ng/ml pertussis toxin did not prevent CCK-8 from evoking cationic currents. Internal administration of heparin (2 mg/ml), an inositol 1,4,5-trisphosphate (IP3) receptor antagonist, and buffering of intracellular calcium with the Ca(2+)-chelator, BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, 10 mM), suppressed CCK-8-evoked cationic currents. These findings suggest that, by activating CCKB receptors, CCK-8 excites rat neostriatal neurons through enhancing a non-selective cationic conductance and that pertussis toxin-insensitive G-proteins mediate CCK-8 enhancement of the cationic conductance. The coupling mechanism via G-proteins is likely to involve the production of IP3, and the subsequent IP3-evoked Ca2+ release leads to the opening of non-selective cation channels.
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PMID:The excitatory effect of cholecystokinin on rat neostriatal neurons: ionic and molecular mechanisms. 883 13

In this study we determined the changes in the intracellular free Ca2+ concentration, associated with the inhibitory modulation of the exocytotic release of GABA by GABAB receptor activation in rat cerebrocortical synaptosomes. We observed that SK&F 97541 and (-)baclofen both act as agonists of the presynaptic GABAB receptors in modulating GABA release and Ca2+ influx due to KCl (10 mM) depolarization, but SK&F 97541 is more potent than (-)baclofen in modulating both Ca2+ influx and GABA release. Thus, activation of GABAB receptors by either SK&F97541 (10 microM) or by (-)baclofen (100 microM) caused about 18% inhibition of the increase in [Ca2+]i, due to KCl depolarization, and inhibited the [3H]GABA release by about 30%. The pharmacological similarities of the GABAB receptor activation in producing inhibition of both calcium channel mediated influx of Ca2+ and transmitter release suggest that presynaptic inhibition of GABA release by GABAB receptor activation may result, at least in part, from inhibition of Ca2+ influx through P-type (or possibly Q-type) Ca2+ channels, sensitive to omega-Agatoxin IVA (200 nM). Furthermore, modulation of GABA release of GABAB receptors was abolished by preincubation with pertussis toxin, suggesting that a pertussis toxin sensitive G protein may be the coupling factor between GABAB receptors and the voltage-dependent Ca2+ channels associated with the exocytotic release of GABA in rat cerebrocortical nerve terminals.
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PMID:Regulation of intracellular [Ca2+] and GABA release by presynaptic GABAB receptors in rat cerebrocortical synaptosomes. 884 40

Neurons of the substantia nigra pars reticulata can be readily and fully inhibited by endogenously released or iontophoretically applied GABA. We have previously shown that co-application of dopamine or the D2-like agonist quinpirole causes a current-dependent attenuation of the inhibitory response of these neurons to GABA. To determine if the modulation of GABA responsiveness was mediated by activation of D2 receptors, effects of iontophoretic quinpirole were examined after various treatments which block or inactivate D2 receptors, or uncouple D2 receptors from their G-proteins. Results showed that the GABA-attenuating effect of quinpirole could be attributed to stimulation of D2 receptors, and not a non-specific effect of the drug, since (1) co-iontophoresis of the D2 antagonist YM 09151-2 antagonized the GABA-modulatory effect of quinpirole, (2) prior intranigral injection of the receptor inactivator N-ethoxy-carbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ; 50 nmol/0.5 ml one day before recording) prevented the response to quinpirole, and (3) prior intranigral injection of the Gi-Go-protein inactivator pertussis toxin (1 mg/ml 0.9% NaCl 24 h before recording) completely abolished the ability of quinpirole to lessen the inhibitory response to GABA. The location of the involved D2 receptors was examined using selective lesioning approaches. Kainic acid lesions of the striatonigral pathway did not prevent the ability of quinpirole to attenuate responses of pars reticulata neurons to GABA. Similarly, in previous studies [59], 6-hydroxydopamine lesions of the adjacent pars compacta dopamine neurons were found not to abolish the GABA-attenuating effect of dopamine. Thus, it appears that the receptors mediating the response are not localized to either striatonigral terminals nor to the adjacent dopamine neurons, leaving open the possibility that the response is mediated by D2 receptors located on pars reticulata neurons. Collectively these results suggest that dendritically released dopamine may act via nigral D2 receptors, perhaps located on pars reticulata neurons themselves, to regulate basal ganglia output from the substantia nigra.
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PMID:Dopamine D2, receptor-mediated modulation of the GABAergic inhibition of substantia nigra pars reticulata neurons. 887 84

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