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

The signal transduction and pharmacological properties of a metabotropic glutamate receptor, mGluR1, were studied in CHO cells permanently expressing the cloned receptor. mGluR1 stimulated phosphatidylinositol (PI) hydrolysis in the potency rank order of quisqualate greater than L-glutamate greater than or equal to ibotenate greater than L-homocysteine sulfinate greater than or equal to trans-ACPD. This receptor also evoked the stimulation of cAMP formation and arachidonic acid release with comparable agonist potencies. DL-AP3 and L-AP4, the effective antagonists reported for glutamate-stimulated PI hydrolysis in brain slices, showed no appreciable effects on mGluR1, suggesting the existence of an additional subtype of this receptor family. Pertussis toxin and phorbol ester produced distinct effects on the three transduction cascades, implying that mGluR1 independently links to the multiple transduction pathways probably through different G proteins.
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PMID:Signal transduction and pharmacological characteristics of a metabotropic glutamate receptor, mGluR1, in transfected CHO cells. 131 23

In primary cultured striatal neurons we found that (+-)-trans-1-amino-cyclopentyl-1,3-dicarboxylate (trans-ACPD) could inhibit forskolin-induced cAMP formation in a dose-dependent manner (EC50 156 +/- 38 microM, n = 5, maximal inhibition 37.8 +/- 1.2, n = 37). The trans-ACPD-induced inhibition was totally abolished in neurons preincubated with Bordetella pertussis toxin (1 microgram/ml), demonstrating the involvement of a G-protein. This is the first report in intact neurons of a glutamate metabotropic receptor negatively coupled to cAMP formation.
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PMID:Trans-ACPD inhibits cAMP formation via a pertussis toxin-sensitive G-protein. 132 80

1. 2S,3S,4S-2-(carboxycyclopropyl)glycine (L-CCG-I), a conformationally restricted glutamate analogue, is a potent metabotropic L-glutamate receptor agonist in the mammalian central nervous system. 2. Depolarizing actions of L-CCG-I and trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD) in the newborn rat spinal motoneurone are temperature-sensitive, and are not depressed by 3-[(+/-)-2-carboxypiperazin-4-yl] propyl-1-phosphonic acid (CPP) and/or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). 3. L-CCG-I and trans-ACPD induced oscillatory responses in Xenopus oocytes injected with rat brain mRNA. Oocytes with oscillatory responses to L-CCG-I and trans-ACPD showed reversal potential of about -20 mV, which was very close to the equilibrium potential of chloride ions. 4. In rat hippocampal synaptoneurosomes, L-CCG-I stimulated phosphoinositide hydrolysis in a concentration dependent manner. L-CCG-I was less potent than quisqualate but more potent than trans-ACPD. 5. At low concentrations, L-CCG-I did not cause any depolarization of newborn rat spinal motoneurones, but reduced substantially amplitudes of monosynaptic reflexes. 6. At the crayfish neuromuscular junction L-CCG-I, acting presynaptically, reduced the amplitude of excitatory junctional potentials. This action was prevented by application of picrotoxin but not pertussis toxin. The actions of trans-ACPD differ from those of either L-CCG-I or ibotenate at the crayfish neuromuscular junction. 7. L-CCG-I has a potential to provide further useful information on metabotropic L-glutamate receptor function.
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PMID:A metabotropic L-glutamate receptor agonist: pharmacological difference between rat central neurones and crayfish neuromuscular junctions. 136 Mar 66

Pharmacological studies of glutamate receptor stimulation of the phosphoinositide (PI) system have demonstrated that this response is blocked by several agents: 2-amino-3-phosphonopropionate (AP3), phorbol esters and in some preparations pertussis toxin. In electrophysiological studies of CA1 pyramidal neurons, we have found that pertussis toxin and AP3 (1-2 mM) do not block either the membrane depolarization or inhibition of the slow afterhyperpolarization elicited by trans-1-aminocyclopentyl-1,3-dicarboxylate (ACPD; 30 microM), a selective agonist of the PI-linked glutamate receptor. However, phorbol 12,13-diacetate (1-1.5 microM) which itself blocks the slow afterhyperpolarization, completely blocks the membrane depolarizing response elicited by ACPD. These results add to growing evidence for heterogeneity among PI-linked glutamate receptor responses.
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PMID:Pharmacological characterization of phosphoinositide-linked glutamate receptor excitation of hippocampal neurons. 196 52

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

In this study, the regulation of striatal cyclic-3',5'-adenosine monophosphate (cAMP) formation and GABA release by dopamine D1 and metabotropic glutamate receptors (mGluR) was studied in brain slices. In the absence of adenosine A2 receptor blockade, the mGluR agonist, 1-aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R-ACPD) stimulated cAMP accumulation through a pertussis toxin-insensitive mechanism that could be blocked by L-serine-o-phosphate, but not by L(+)-2-amino-3-phosphonopropionic acid. However, in the presence of the adenosine antagonist, 3-isobutyl-1-methylxanthine, 1S,3R-ACPD had no significant effect on basal cAMP, but it inhibited cAMP formation stimulated by the D1 agonist, SKF 38393. This inhibitory response was prevented by pertussis toxin pretreatment and mimicked by L(+)-2-amino-3-phosphonopropionic acid, but it was unaffected by L-serine-o-phosphate. Thus, 1S,3R-ACPD was determined to activate distinct mGluRs in the striatum that mediate either inhibition or activation of cAMP accumulation, with the latter effect being dependent on the activation of adenosine A2 receptors. A potential physiological role for the interaction between the D1 and adenosine-dependent stimulatory metabotropic receptor was sought by examining this interaction on striatal GABA release. SKF 38393 and 1S,3R-ACPD together were found to potentiate striatal GABA release induced by 15 mM K+. The potentiation was blocked by the D1 antagonist, SCH 23390. However, this effect was only partially mimicked by a high concentration of forskolin (100 microM) and was not blocked by L-serine-o-phosphate, thereby suggesting that the stimulatory mGluR does not mediate this potentiation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of striatal cyclic-3',5'-adenosine monophosphate accumulation and GABA release by glutamate metabotropic and dopamine D1 receptors. 747 79

We have reported previously that a selective metabotropic glutamate receptor agonist, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), caused two primary postsynaptic membrane changes, namely, a slow membrane depolarization, and burst firing in rat dorsolateral septal nucleus neurons. In addition, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid also potentiates a slow after depolarization in rat dorsolateral septal nucleus neurons. We now report that, among all the postsynaptic membrane changes induced by (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid, only the burst firing was selectively blocked by pertussis toxin pretreatment. Thus, aminocyclopentane-1,3-dicarboxylic acid induced burst firing was mediated by a metabotropic receptor coupled to a pertussis toxin-sensitive GTP-binding protein, while the other induced cellular responses may be mediated by metabotropic glutamate receptors insensitive to pertussis toxin. We further characterized this receptor pharmacologically. This metabotropic receptor is activated by several metabotropic glutamate receptor agonists, but is insensitive to L-glutamate or L-aspartate. On the basis of its agonist activity profile, particularly the ineffectiveness of glutamate as an agonist, we have tentatively assigned the name aminocyclopentane-1,3-dicarboxylic acid metabotropic receptor, to this native, pertussis toxin-sensitive metabotropic receptor in the dorsolateral septal nucleus. Furthermore, this receptor is coupled to protein kinase C, probably via a phospholipase C independent pathway.
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PMID:(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid-induced burst firing is mediated by a native pertussis toxin-sensitive metabotropic receptor at rat dorsolateral septal nucleus neurons. 747 53

Glutamate induced an increase in cell volume within one minute and evoked cytosolic Ca2+ transients in type 1 astroglial cells in primary culture obtained from the cerebral cortex of newborn rat. Even the metabotropic glutamate receptor agonists (1S,3R)-1-aminocyclopentane- 1,3-dicarboxylic acid (1S-3R-ACPD) and L(+)-2-amino-4 phosphonobutyric acid (L-AP4) induced a cell swelling with ACPD inducing a parallel Ca2+ transient while L-AP4 did not. A new method was used where rapid changes in relative cell volume could be followed at the single cell level. Relative volume changes in cultured single astroglial cells were examined by microspectrofluorimetry after loading the cells with the highly fluorescent intracellular probe fura-2/AM. At its isosbestic point, 358 nm, fura-2 is ion-insensitive and the fluorescent signals emitted are related only to the intracellular dye concentration. By varying the excitation wavelengths, changes in intracellular Ca2+ transients could be recorded simultaneously with the relative volume variations of the individual cells. Thus, as rapid changes in cell volume were followed, the results from this method could be of physiological significance. Glutamate-induced cell swelling was blocked by BaCl2 and by tetraethylammonium, suggesting that K+ channels are operative in glutamate-induced cell swelling. Furthermore, the glutamate-induced swelling was blocked by the Na+; K+, and 2Cl- co-transport inhibitor furosemide. The glutamate-induced swelling was partially blocked by pertussis toxin and partially blocked also by the glutamate carrier-blocker dihydroaspartate. When the ionotropic glutamate receptor alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid was blocked with the antagonist 2,3-dihydroxy-6-nitro-7- sulfamoyl-benzo(F)quinoxaline, glutamate still induced a swelling, suggesting that this receptor was not directly involved in the glutamate-induced volume increase. Even in situations of blocked or partially blocked swelling, intracellular Ca2+ transients could be obtained. Furthermore, the glutamate-induced swelling was evoked even in low extracellular Ca2+ concentrations. Our data suggest that glutamate-induced rapid swelling is a complex process at the molecular level. One hypothetical mechanism might be that glutamate interacts with metabotropic glutamate receptors and induces a release of Ca2+ from internal stores. Furthermore glutamate interacts with K+ channels, and probably at least one co-transporter and the sodium-dependent high-affinity uptake glutamate carrier, resulting in cell swelling.
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PMID:Glutamate-induced swelling of single astroglial cells in primary culture. 753 92

1. The effects of metabotropic glutamate receptor (mGluR) agonists on excitatory postsynaptic potentials (EPSPs) evoked by stimulation of mossy fibers (MF) and parallel fibers (PF) were examined in turtle cerebellar Purkinje cells. 2. The mGluR agonist 1S,3R-ACPD (1-25 microM) reversibly potentiated the amplitude of the MF-evoked EPSPs, but was without effect on PF-evoked EPSPs. The potentiation of MF-evoked EPSPs was dose-dependent, with a median effective dose (ED50) of approximately 4.4 microM. At higher doses (15-25 microM) 1S,3R-ACPD produced a direct depolarization of Purkinje cells in 58% of cells examined. 3. The enhancement of MF EPSPs by 1S,3R-ACPD was mimicked by 1S,3S-ACPD (50 microM) and blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovalerate (D-AP5), but not by the mGluR antagonist L-2-amino-3-phosphonopionic acid (L-AP3; 1 mM), or the 1R,3S isomer of ACPD (25-500 microM). 4. Quisqualate (1 microM) produced a biphasic effect on MF EPSPs, producing an initial blockade of the EPSP followed by a D-AP5-sensitive potentiation. 5. The potentiation of MF EPSPs by 1S,3R-ACPD was not blocked by prior exposure to the protein kinase C activator phorbol 12-myristate 13-acetate (10 microM), the protein kinase C inhibitor calphostin C (1 microM), the adenylate cyclase activator forskolin (25 microM), or the nitric oxide donator sodium nitroprusside (1 mM). Preincubation of the tissue for 24-48 h in pertussis toxin also failed to prevent the ability of 1S,3R-ACPD to potentiate the NMDA receptor-mediated component of the MF EPSP. PF EPSPs were also not significantly affected by these agents. 6. The results demonstrate that the mGluR agonists 1S,3R-ACPD, 1S,3S-ACPD, and quisqualate produce a potent, stereospecific potentiation of NMDA receptor-mediated transmission at the MF-granule cell synapse. Agents that modulate the intracellular messengers protein kinase C, adenylate cyclase, nitric oxide, or pertussis toxin-sensitive G proteins failed to mimic or block this effect. This would suggest that the potentiation of NMDA receptor-mediated transmission at this synapse is not mediated via these systems, and reflects a different site of action of mGluR agonists on the NMDA receptor. The observed interaction between mGluR and NMDA receptors in granule cells provides a means for activity-dependent modulation of synaptic transmission, which may play a role in synaptic integration at the MF-granule cell synapse.
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PMID:Potentiation of NMDA receptor-mediated transmission in turtle cerebellar granule cells by activation of metabotropic glutamate receptors. 768 76

The ability of excitatory amino acids to stimulate phosphoinositide hydrolysis in mouse cerebellar granule cells was characterized. Quisqualic acid (EC50 = 2 microM), ibotenic acid (EC50 = 15 microM), kainic acid (EC50 = 30 microM), glutamate (EC50 = 51 microM) and (1S,3R)-1-amino-cyclo-pentane-1,3-dicarboxylic acid (t-ACPD) (EC50 = 175 microM) dose-dependently stimulated phosphoinositide hydrolysis. The stimulation of phosphoinositide hydrolysis was dose-dependently blocked by 2-amino-3-phosphonopropionic acid (L-AP3) and pertussis toxin, but was unaffected by other excitatory amino acid agonists or antagonists. These data suggest that the pharmacology of excitatory amino acid-stimulated phosphoinositide hydrolysis in the mouse cerebellar granule cells is mediated through the G protein coupled metabotropic glutamate receptor. The overall pharmacology of the metabotropic receptor present in mouse cerebellar granule cells differs from that of previously reported tissue preparations such as rat cerebellar granule cells. In addition, the effect of the alpha-amino-3-hydroxyl-5-methyl-1-isoxazole-4-propionic acid (AMPA) receptor antagonist, 2,3-dihydroxy-6-nitro-7-sulphamoylbenzo(F)quinoxaline (NBQX), on excitatory amino acid-stimulated phosphoinositide hydrolysis was also examined. NBQX was without effect on either basal phosphoinositide hydrolysis or excitatory amino acid-stimulated phosphoinositide hydrolysis, suggesting that the neuroprotective effect of NBQX is not mediated through the metabotropic glutamate receptor.
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PMID:Characterization of the metabotropic glutamate receptor in mouse cerebellar granule cells: lack of effect of 2,3-dihydroxy-6-nitro-7-sulphamoylbenzo(F)-quinoxaline (NBQX). 768 59


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