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)

Three major subtypes of glutamate receptors that are coupled to cation channels--N-methyl-D-aspartate (NMDA), kainate, and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors--are known as ionotropic receptors in the mammalian CNS. Recently, an additional subtype that is coupled to GTP binding proteins and stimulates (or inhibits) metabolism of phosphoinositides has been proposed as a metabotropic receptor. Incubation of dispersed hippocampal cells from adult rats with glutamate or NMDA decreased forskolin-stimulated cyclic AMP (cAMP) accumulation; half-maximal effects were obtained with 5.6 +/- 2.2 and 6.4 +/- 2.3 microM, respectively. Kainate and quisqualate were less potent. The effect of glutamate was antagonized by 2,3-diaminopropionate and 2-amino-5-phosphonovalerate, NMDA/glutamate receptor antagonists, but not by 0.5 microM Joro spider toxin, a specific blocker of the AMPA receptor. The inhibitory effect of glutamate on cAMP formation was not blocked by 2 microM tetrodotoxin or by the absence of Ca2+. In hippocampal membranes, glutamate, similar to carbachol, inhibited adenylate cyclase activity in a GTP-dependent manner. These findings suggest that the glutamate inhibition of adenylate cyclase is direct and is not due to a result of the release of other neurotransmitters. The effect of glutamate on cAMP accumulation was observed in an assay medium containing 0.7 mM MgCl2, which is known to inhibit both ionotropic NMDA receptor/channels in the hippocampus and metabotropic NMDA receptors in the cerebellum. The inhibitory effect of glutamate was abolished by pertussis toxin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glutamate inhibits adenylate cyclase activity in dispersed rat hippocampal cells directly via an N-methyl-D-aspartate-like metabotropic receptor. 135 90

Guanine nucleotides have been examined as to their effects on subclass-specific excitatory amino acid receptor-ligand interactions. Guanine nucleotides selectively inhibit L-[3H]glutamate binding to the N-methyl-D-aspartate (NMDA) recognition site while showing a lesser effect on [3H]kainate, [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate and sodium-dependent L-[3H]glutamate binding. Of the series of guanine nucleotides tested in the inhibition of NMDA-specific L-[3H]glutamate binding, GTP, GDP, 5'-guanylylimidodiphosphate and 5'-guanylylmethylenediphosphate were significantly more potent than GMP, cyclic GMP and guanosine. Scatchard analysis indicates that the GTP inhibition (IC50 = 28 microM) of this NMDA-specific L-[3H]glutamate binding results from a decrease in the affinity of L-glutamate for the NMDA receptor whereas no alteration in the number of binding sites is observed. A kinetic analysis indicates that this decrease in affinity may be attributed to a decrease in association rate whereas no change in dissociation rate is observed. GTP (25 microM) lowers the affinities of both NMDA agonists (NMDA, L-glutamate, L-aspartate, and L-homocysteate) and antagonists (D-2-amino-5-phosphonovalerate, D-2-amino-7-phosphonoheptanoate, and D-2-aminoadipate). Pretreatment of the synaptic plasma membranes with either pertussis or cholera toxin had no significant effect on the GTP inhibition of NMDA-specific L-[3H] glutamate binding. The data suggest that guanine nucleotides can negatively modulate the NMDA receptor; however, the mechanism of this modulation is unclear.
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PMID:Effects of guanine nucleotides on N-methyl-D-aspartate receptor-ligand interactions. 284 50

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

1. The effect of dopamine (DA) on the excitatory synaptic transmission was studied in the CA1 neurons of rat hippocampal slices using intracellular recording technique. 2. Depolarizing excitatory postsynaptic potentials (EPSPs) were evoked by stimulation of the Schaffer collateral-commissural pathway. Superfusion of DA (0.03-1 microM) reversibly decreased the EPSP in a concentration-dependent manner and with an estimated IC50 of 0.3 microM. The sensitivity of postsynaptic neurons to the glutamate-receptor agonists, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid or N-methyl-D-aspartate was unchanged by DA (0.3 microM) pretreatment. In addition, DA (0.3 microM) increased the magnitude of paired-pulse facilitation, a phenomenon attributed to an increase in the amount of transmitter released in response to the second stimulus. 3. The reduction of DA (0.3 microM) on the EPSP was antagonized by sulpiride (1-10 nM), a selective D2-receptor antagonist. However, D1-receptor antagonist, SKF-83566 (1-10 microM), did not significantly affect the reduction of DA (0.3 microM) on the EPSP. 4. (+/-)-2-(N-Phenylethyl-N-propyl)amino-5-hydroxytetralin (1 microM), an agonist of D2 receptor, mimicked the inhibitory effect of DA on the EPSP. However, neither the D1-receptor agonist SKF-38393 (1 microM) nor the D3-receptor agonist (PD-128,907 (1 microM) affected the EPSP. 5. Incubation of hippocampal slices with pertussis toxin (PTX, 5 micrograms/ml) for 12 h prevented the reduction of EPSP induced by DA (0.3 microM). 6. Rp-adenosine-3',5'-cyclic monophosphothioate (25 microM), a potent inhibitor of protein kinase A (PKA), alone decreased the amplitude of EPSP below baseline values and prevented the subsequent reduction by DA (0.3 microM). 7. These results indicate that DA at a low concentration (< or = 0.3 microM) reduces the excitatory response of hippocampal CA1 neurons after synaptic stimulation via the activation of presynaptic D2 receptors. The presynaptic action of DA is mediated by a PTX-sensitive Gi-proteins-coupled to PKA pathway.
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PMID:Characterization of dopamine receptors mediating inhibition of excitatory synaptic transmission in the rat hippocampal slice. 889 Mar 1

Excitatory synaptic transmission in the central nervous system is mediated primarily by the release of glutamate from presynaptic terminals onto postsynaptic channels gated by N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors. The myriad intracellular responses arising from the activation of the NMDA and AMPA receptors have previously been attributed to the flow of Ca2+ and/or Na+ through these ion channels. Here we report that the binding of the agonist AMPA to its receptor can generate intracellular signals that are independent of Ca2+ and Na+ in rat cortical neurons. In the absence of intracellular Ca2+ and Na+, AMPA, but not NMDA, brought about changes in a guanine-nucleotide-binding protein (Galpha[il]) that inhibited pertussis toxin-mediated ADP-ribosylation of the protein in an in vitro assay. This effect was observed in intact neurons treated with AMPA as well as in isolated membranes exposed to AMPA, and was also found in MIN6 cells, which express functional AMPA receptors but have no metabotropic glutamate receptors. AMPA also inhibited forskolin-stimulated activity of adenylate cyclase in neurons, demonstrating that Gi proteins were activated. Moreover, both Gbetagamma blockage and co-precipitation experiments demonstrated that the modulation of the Gi protein arose from the association of Galpha(il) with the glutamate receptor-1 (GluR1) subunit. These results suggest that, as well as acting as an ion channel, the AMPA receptor can exhibit metabotropic activity.
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PMID:AMPA receptor-mediated regulation of a Gi-protein in cortical neurons. 2925 99

1. The metabotropic glutamate receptor (mGluR) agonist trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD) (10-100 microM) depolarized isolated frog spinal cord motoneurones, a process sensitive to kynurenate (1.0 mM) and tetrodotoxin (TTX) (0.783 microM). 2. In the presence of NMDA open channel blockers [Mg2+; (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK801); 3,5-dimethyl-1-adamantanamine hydrochloride (memantine)] and TTX, trans-ACPD significantly potentiated NMDA-induced motoneurone depolarizations, but not alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA)- or kainate-induced depolarizations. 3. NMDA potentiation was blocked by (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) (240 microM), but not by alpha-methyl-(2S,3S,4S)-alpha-(carboxycyclopropyl)-glycine (MCCG) (290 microM) or by alpha-methyl-(S)-2-amino-4-phosphonobutyrate (L-MAP4) (250 microM), and was mimicked by 3,5-dihydroxyphenylglycine (DHPG) (30 microM), but not by L(+)-2-amino-4-phosphonobutyrate (L-AP4) (100 microM). Therefore, trans-ACPD's facilitatory effects appear to involve group I mGluRs. 4. Potentiation was prevented by the G-protein decoupling agent pertussis toxin (3-6 ng ml(-1), 36 h preincubation). The protein kinase C inhibitors staurosporine (2.0 microM) and N-(2-aminoethyl)-5-isoquinolinesulphonamide HCI (H9) (77 microM) did not significantly reduce enhanced NMDA responses. Protein kinase C activation with phorbol-12-myristate 13-acetate (5.0 microM) had no effect. 5. Intracellular Ca2+ depletion with thapsigargin (0.1 microM) (which inhibits Ca2+/ATPase), 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetracetic acid acetyl methyl ester (BAPTA-AM) (50 microM) (which buffers elevations of [Ca2+]i), and bathing spinal cords in nominally Ca2+-free medium all reduced trans-ACPD's effects. 6. The calmodulin antagonists N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W7) (100 microM) and chlorpromazine (100 microM) diminished the potentiation. 7. In summary, group I mGluRs selectively facilitate NMDA-depolarization of frog motoneurones via a G-protein, a rise in [Ca2+]i from the presumed generation of phosphoinositides, binding of Ca2+ to calmodulin, and lessening of the Mg2+-produced channel block of the NMDA receptor.
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PMID:Mechanisms involved in the metabotropic glutamate receptor-enhancement of NMDA-mediated motoneurone responses in frog spinal cord. 1005 Nov 53

We examined actions of arginine vasopressin (AVP) and amastatin (an inhibitor of the aminopeptidase that cleaves AVP) on synaptic currents in slices of rat parabrachial nucleus using the nystatin-perforated patch recording technique. AVP reversibly decreased the amplitude of the evoked, glutamate-mediated, excitatory postsynaptic current (EPSC) with an increase in paired-pulse ratio. No apparent changes in postsynaptic membrane properties were revealed by ramp protocols, and the inward current induced by a brief application of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid was unchanged after AVP. The reduction induced by 1 microM AVP could be blocked by a V(1) AVP receptor antagonist, [d(CH(2))(5)(1)-O-Me-Tyr(2)-Arg(8)]-vasopressin (Manning compound, 10 microM). Bath application of an aminopeptidase inhibitor, amastatin (10 microM), reduced the evoked EPSC, and AVP induced further synaptic depression in the presence of amastatin. Amastatin's effects also could be antagonized by the Manning compound. Corticotropin-releasing hormone slightly increased the EPSC at 1 microM, and coapplication with AVP attenuated the AVP response. Pretreatment of slices with 1 microg/ml cholera toxin or 0.5 microg/ml pertussis toxin for 20 h did not significantly affect AVP's synaptic action. The results suggest that AVP has suppressant effects on glutamatergic transmission by acting at V(1) AVP receptors, possibly through a presynaptic mechanism involving a pertussis-toxin- and cholera-toxin-resistant pathway.
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PMID:Vasopressin and amastatin induce V(1)-receptor-mediated suppression of excitatory transmission in the rat parabrachial nucleus. 1051 59

The present study was designed to characterize the possible roles of spinally located cholera toxin (CTX)- and pertussis toxin (PTX)-sensitive G-proteins in excitatory amino acids induced pain response. Intrathecal (i.t.) injection of glutamate (20 microg), N-methyl-D-aspartic acid (NMDA; 60 ng), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA; 13 ng), and kainic acid (12 ng) showed pain response. Pretreatment with CTX (0.05 and 0.5 microg, i.t.) attenuated pain response induced by glutamate, NMDA, AMPA and kainic acid administered i.t. in a dose-dependent manner. On the other hand, i.t. pretreatment with PTX further increased the pain response induced by glutamate, NMDA, AMPA and kainic acid administered i.t., especially at the dose of 0.5 microg. Our results suggest that, at the spinal cord level, CTX- and PTX-sensitive G-proteins appear to play opposite roles in modulating the pain response induced by spinally administered. Furthermore, CTX- and PTX-sensitive G-proteins appear to modulate pain response induced by stimuli of both NMDA and non-NMDA glutamate receptors.
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PMID:Differential modulatory roles of cholera toxin and pertussis toxin in the regulation of pain responses induced by excitatory amino acids administered intrathecally in mice. 1083 21

The striatum is a crucial site of action for the motor effects of cannabinoids (CBs). However, the electrophysiological consequences of activation of CB receptors on the striatal neurons have not been established. Here we report for the first time that the cannabimimetic aminoalkylindole WIN 55,212-2 and the endogenous cannabinoid anandamide substantially depress corticostriatal glutamatergic synaptic transmission onto striatal neurons in the brain slice preparation. The selective CB1 receptor antagonist SR 141716 effectively reversed this inhibition. WIN 55,212-2 significantly increased the paired-pulse facilitation of synaptically evoked EPSCs, while having no effect on the sensitivity of postsynaptic neurons to [alpha]-amino-3-hydroxy-5-methylisoxazole-4-propionic acid. WIN 55,212-2 also reduced the frequency of spontaneous, action potential-dependent EPSCs (sEPSCs) without altering their amplitude distribution. Superfusion of WIN 55,212-2 elicited a membrane hyperpolarization accompanied by a decrease in input resistance. Both effects were blocked by intracellular caesium. In contrast, intracellular caesium failed to affect WIN 55,212-2-mediated synaptic inhibition. The WIN 55,212-2-mediated synaptic inhibition was blocked by the Gi/o protein inhibitor pertussis toxin (PTX), but not by the GABA(A) receptor antagonist bicuculline or GABA(B) receptor antagonist SCH 50911. Pretreatment with the N-type Ca2+ channel antagonist [omega]-conotoxin GVIA selectively abolished the WIN-55,212-2-mediated synaptic inhibition. These results suggest that cannabinoids depress the corticostriatal glutamatergic synaptic transmission through the activation of presynaptic CB1 receptors to inhibit N-type Ca2+ channel activity, which in turn reduces glutamate release. The presynaptic action of cannabinoids is mediated by a PTX-sensitive Gi/o protein-coupled signalling pathway.
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PMID:Presynaptic mechanisms underlying cannabinoid inhibition of excitatory synaptic transmission in rat striatal neurons. 1131 42

Pregnenolone sulfate (PREGS), one of the most abundantly produced neurosteroids in the mammalian brain, improves cognitive performance in rodents. The mechanism of this effect has been attributed to its allosteric modulatory actions on glutamate- and gamma-aminobutyric acid-gated ion channels. Here we report a novel effect of PREGS that could also mediate some of its actions in the nervous system. We found that PREGS induces a robust potentiation of the frequency but not the amplitude of miniature excitatory postsynaptic currents (mEPSCs) mediated by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors in cultured hippocampal neurons. PREGS also decreased paired pulse facilitation of autaptic EPSCs evoked by depolarization, indicating that it modulates glutamate release probability presynaptically. PREGS potentiation of mEPSCs was mimicked by dehydroepiandrosterone sulfate and (+)-pentazocine but not by (-)-pentazocine, the synthetic (-)-enantiomer of PREGS or the inactive steroid isopregnanolone. The sigma receptor antagonists, haloperidol and BD-1063, blocked the effect of PREGS on mEPSCs, as did pertussis toxin and the membrane-permeable Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (acetoxymethyl) ester. These results suggest that PREGS increases spontaneous glutamate release via activation of a presynaptic G(i/o)-coupled sigma receptor and an elevation in intracellular Ca2+ levels. We postulate that presynaptic actions of neurosteroids have a role in the maturation and/or maintenance of synaptic networks and the processing of information in the central nervous system.
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PMID:Neurosteroids enhance spontaneous glutamate release in hippocampal neurons. Possible role of metabotropic sigma1-like receptors. 1204 5

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