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)

We have previously reported that the response of cultured chick cerebellar neurons to glutamate is enhanced by noradrenaline (NA) or isoproterenol and suppressed by clonidine. The present study was carried out to further specify the adrenergic receptor subtypes involved in the facilitatory effect of NA or isoproterenol and the suppressive effect of clonidine, and to examine the intracellular mechanisms underlying these modulatory effects of NA. The clonidine effect, which was mimicked by NA iontophoresed with large ejecting currents, was blocked by yohimbine and tolazoline (alpha 2 antagonists) and also by dibutyryl cyclic AMP or forskolin which augmented the glutamate response by itself. Prazosin, an alpha 1 receptor antagonist did not block the clonidine effect. NA- or isoproterenol-induced facilitation, which was mimicked by denopamine (beta 1 agonist), was antagonized by acebutolol (beta 1 antagonist) and not by ICI 118,551 (beta 2 antagonist). Pretreatment of neurons with pertussis toxin for more than 24 h blocked the suppressive action of clonidine without affecting the facilitatory action of isoproterenol. Furthermore, intracellular injection of GDP beta S inhibited the modulatory effects of either clonidine or isoproterenol. These results indicate that the facilitatory and inhibitory modulatory effects of NA may be mediated by beta 1 and alpha 2 receptors linked to cAMP systems, respectively, and the former is coupled with the stimulatory G protein (Gs) and the latter is with the inhibitory G protein (Gi).
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PMID:Subtypes of adrenergic receptors and intracellular mechanisms involved in modulatory effects of noradrenaline on glutamate. 167 79

The hydrolysis of phosphoinositides (PI) elicited in cerebellar granule cell cultures by agonists of metabolotropic glutamate receptors, glutmate and quisqualate, was enhanced when the cells were pretreated with concanavalin A (Con-A). A similar effect was produced by wheat germ agglutinin, but not by several other lectins tested. Con-A produced a dose-dependent effect (EC50 = 3 microM) and increased the efficacy but not the potency of the agonists. In contrast, Con-A failed to enhance PI hydrolysis evoked by N-methyl-D-aspartate, kainate, carbachol, the calcium ionophore A23187, or 50 mM K+. The Con-A stimulatory effect was prevented by simultaneous pretreatment with the agonists of ionotropic quisqualate receptors quisqualate, kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, but not by the antagonist 6-cyano-7-nitroquioxaline-2,3-dione (CNQX). CNQX, which did not inhibit quisqualate-stimulated PI hydrolysis in untreated cells, abolished the component of quisqualate response enhanced by Con-A pretreatment. The pretreatment with Con-A also increased the influx of 45Ca2+ in granule cells stimulated by quisqualate. This increase was inhibited by CNQX. Moreover, the potentiation of PI hydrolysis by Con-A, but not the response to quisqualate alone, was abolished in the absence of Ca2+ and Na+. Pretreatment of granule cells with pertussis toxin inhibited PI hydrolysis stimulated by the metabolotropic quisqualate receptor and the Con-A-potentiated response by the same percentage, but Ca2+ influx induced by quisqualate was not affected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pretreatment of cerebellar granule cells with concanavalin A potentiates quisqualate-stimulated phosphoinositide hydrolysis. 167

In cerebellar granule cells, baclofen acted with micromolar concentrations at proposed gamma-aminobutyric acid-B receptors to inhibit the formation of cyclic AMP and depolarization-induced release of glutamate. Nanomolar concentrations of baclofen inhibited depolarization-induced influx of calcium. All three responses to baclofen were attenuated after pertussis toxin pretreatment of cell cultures. The inhibition of calcium influx and glutamate release were reversed by the cyclic AMP analog, 8-(4-chlorphenylthio)-cyclic AMP. The release of glutamate was dependent on the influx of extracellular calcium, which enters the cell through dihydropyridine-sensitive voltage-dependent calcium channels. Because the decrease in calcium influx by baclofen and nifedipine were additive, the baclofen-mediated decrease in calcium influx may not involve a dihydropyridine-sensitive calcium channel. These results show similarities between the baclofen-mediated inhibition of cyclic AMP formation and glutamate release, suggesting a relationship between these two events. The baclofen-mediated inhibition of calcium influx may not be related to baclofen's inhibition of glutamate release.
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PMID:gamma-Aminobutyric acid-B receptors inhibit glutamate release from cerebellar granule cells: consequences of inhibiting cyclic AMP formation and calcium influx. 167 50

As previously shown with adenosine, somatostatin, which is ineffective alone, enhanced the alpha 1-adrenergic-agonist-stimulated production of inositol phosphates in cultured striatal astrocytes. This effect was suppressed in cells pretreated with pertussis toxin. It required external calcium and was selectively antagonized by both mepacrine, an inhibitor of phospholipase A2, and 5,8,11,14-eicosatetraynoic acid, a nonmetabolizable analog of arachidonic acid. In addition, a long-lasting elevation of cytosolic calcium and a release of arachidonic acid were observed only under the combined stimulation of somatostatin and alpha 1-adrenergic receptors. Arachidonic acid could in turn inhibit glutamate uptake into astrocytes, and the resulting external accumulation of glutamate could account for the somatostatin-evoked amplification of the alpha 1-adrenergic-agonist-stimulated hydrolysis of inositol-phospholipids. The effect of somatostatin was indeed reproduced by glutamate or glutamate uptake inhibitors and suppressed by enzymatic removal of external glutamate. Thus, astrocytes may contribute to long-term plasticity events in glutamatergic synapses through regulation of external glutamate levels.
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PMID:Somatostatin potentiates the alpha 1-adrenergic activation of phospholipase C in striatal astrocytes through a mechanism involving arachidonic acid and glutamate. 168 48

A large number of neurotransmitters have now been shown to reduce the amplitude and slow the activation kinetics of whole cell HVA ICa in a great diversity of neurons. These transmitters include L-glutamate (AMPA/kainate, metabotropic and NMDA receptors), GABA (via GABAB receptors, NA (via alpha 2 receptors), 5-HT, NA (via alpha 2 receptors), DA and several peptides. Both whole-cell and single-channel studies have demonstrated that the N-channel is the most common channel type to be blocked by transmitters, although an inhibition of the L-type channel has also occasionally been reported. The suppression of the N-type Ca current was commonly shown to be voltage-dependent, with a relief at large positive voltages. Strong evidence has been put forward showing that the transmitter action is mediated by a G-protein, with GDP-beta-S blocking transmitter action, and GTP-gamma-S directly inhibiting the Ca channel. Moreover, pertussis toxin blocked the transmitter action in most neurons, and following such block, injection of the G-protein Go restored transmitter action. A direct link between the G-protein and the Ca channel has been widely theorized to mediate the action of transmitters on certain neurons. There is also some evidence that certain transmitters in specific neurons mediate calcium channel inhibition through a 2nd messenger, perhaps protein kinase C. Transmitters have also been found, although uncommonly, to inhibit HVA L-type and LVA T-type channels. In addition, an enhancement of both HVA and LVA Ca currents by transmitters has been demonstrated, and substantial evidence exists for mediation of this action by cAMP.
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PMID:Modulation of vertebrate neuronal calcium channels by transmitters. 168 17

The effects of baclofen microinjected into the nucleus tractus solitarii (NTS) on blood pressure, heart rate and baroreflex bradycardia were studied in urethane-anesthetized rats. Baclofen caused dose-dependent pressor and tachycardic effects and inhibited the reflex bradycardia elicited by i.v. phenylephrine. The effects of baclofen were inhibited by similarly administered GABAB receptor antagonists, phaclofen and 2-OH-saclofen, or the non-NMDA glutamate receptor antagonist, DNQX, or by pretreatment of rats with intracisternally administered pertussis toxin. DNQX and pertussis toxin, but not the NMDA antagonist, MK-801, also inhibited baroreflex bradycardia. Intra-NTS injections of glutamate caused hypotension and bradycardia, which were potentiated by baclofen, and were not affected by either DNQX or MK-801 or by pretreatment with pertussis toxin. These findings indicate that the cardiovascular effects of stimulation of GABAB receptors in the NTS are due, at least in part, to inhibition of the depressor baroreflex response. Inhibition of the release and/or postsynaptic action of an excitatory amino acid transmitter other than glutamate is the most likely mechanism.
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PMID:Mechanism of the cardiovascular effects of GABAB receptor activation in the nucleus tractus solitarii of the rat. 196 70

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

We measured changes in the molar concentration of cytosolic Ca2+ ([Ca2+]i) in individual astrocytes in culture produced by the glutamate analog quisqualate (QA) and related substances by using fura-2 digital fluorescence microscopy. In cells cultured from the cortex, hippocampus, and cerebellum, the QA analog alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA; 10 microM) produced a slow increase in [Ca2+]i that was modest in amplitude (approximately 200 nM). These effects were completely abolished by 10 microM 6-nitro-7-cyano-quinoxaline-2,3-dione (CNQX). In cerebellar astrocytes, similar effects were produced by QA. However, in cortical and hippocampal astrocytes, the response to QA was much more complex. In these cells, QA produced an initial [Ca2+]i spike that was followed by a sustained influx of Ca2+ ("plateau"). In the absence of extracellular Ca2+, this plateau was abolished but the spike remained. CNQX did not block the spike and only slightly reduced the size of the plateau in some cells. Ni2+ (10 microM) but not nimodipine (10 microM) reduced the amplitude of the plateau. Pretreatment with 100 nM phorbol 12-myristate 13-acetate for 15 min abolished the spike but not the plateau portion of the QA response. Treatment with pertussis toxin at 250 ng/ml for 12-16 hr failed to alter the response. In some instances, the latency of the QA response differed considerably for individual cells in a group. It appeared that the response began in one cell and then spread to neighboring cells. Thus, QA appears to trigger a complex response in some astrocytes consisting of Ca2+ mobilization from intracellular stores and also Ca2+ influx resulting from the activation of AMPA-sensitive and -insensitive pathways.
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PMID:Glutamate receptors activate Ca2+ mobilization and Ca2+ influx into astrocytes. 197 Jun 37

Maitotoxin (MTX) stimulated inositol phosphate (IP) formation in primary cultures of rat cerebellar granule cells. MTX-induced IP production was dependent on extracellular Ca2+ but independent of extracellular Na+. The stimulation of IP formation elicited by MTX was unaffected by pretreatment of cells with phorbol dibutyrate, pertussis toxin, and a variety of Ca2+ entry blockers, such as nimodipine, nisoldipine, Co2+, and Mn2+. The presence of MTX markedly attenuated IP production induced by carbachol and glutamate, with no apparent effect on the responses to norepinephrine (NE), histamine, 5-hydroxytryptamine (5-HT), and endothelin-1. The inhibition of the carbachol- and glutamate-induced responses by MTX was dose dependent with IC50 values of 1.2 and 0.5 ng/ml, respectively. Pretreatment of cells with a lower concentration of MTX (0.3 ng/ml) also attenuated carbachol- and glutamate-induced IP formation, in a time-dependent manner, with a decrease observed after 30 min prestimulation, but failed to affect NE-, histamine-, 5-HT-, endothelin-1, and sarafotoxin S6b-induced responses. Thus, MTX elicited a marked Ca2(+)-dependent phosphoinositide (PI) turnover in cerebellar granule cells and selectively inhibited carbachol- and glutamate-induced PI hydrolysis. Possible mechanisms underlying these selective modulations are discussed.
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PMID:Maitotoxin induces phosphoinositide turnover and modulates glutamatergic and muscarinic cholinergic receptor function in cultured cerebellar neurons. 197 55

Proteins can be post-translationally modified by ADP-ribose. Previously, two classes of ADP-ribosyl protein linkages have been detected in vivo which have chemical properties indistinguishable from ADP-ribosyl arginine and ADP-ribosyl glutamate or aspartate. Reported here is the detection of a third class of endogenous ADP-ribosyl protein linkage. This class is chemically indistinguishable from ADP-ribose linked to cysteine residues by a thioglycosidic bond. The distribution of ADP-ribosyl cysteine residues was studied in subcellular fractions of rat liver. Proteins modified on cysteine were detected only in the plasma membrane fraction. Pertussis toxin is known to disrupt signal transduction of ADP-ribosylation of cysteine residues of plasma membrane GTP binding proteins. The results described here raise the interesting possibility that the endogenous modification of plasma membrane protein cysteine residues may be involved in signal transduction.
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PMID:Modification of plasma membrane protein cysteine residues by ADP-ribose in vivo. 211 25


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