Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The AP4 (2-amino-4-phosphonobutyrate) receptor is a presynaptic glutamate receptor that inhibits transmitter release via an unknown mechanism. We examined the action of L-AP4 on voltage-dependent calcium currents and excitatory synaptic transmission on cultured olfactory bulb neurons using whole-cell voltage-clamp methods. In neurons dialyzed with GTP, L-AP4 inhibited high-threshold calcium currents evoked in barium solutions. The inhibition was irreversible in the presence of GTP-gamma-S and blocked by removing intracellular Mg2+ or by preincubation with pertussis toxin (PTX), consistent with the involvement of a PTX-sensitive G-protein. Dialysis with staurosporine or buffering of intracellular calcium to pCa less than 8 did not block the action of L-AP4, suggesting that protein phosphorylation or release of intracellular calcium stores was not involved in calcium current inhibition under these experimental conditions. PTX also blocked the L-AP4-induced inhibition of monosynaptic EPSPs evoked by intracellular stimulation of cultured mitral cells. These results suggest that the presynaptic AP4 receptor is a G-protein-coupled glutamate receptor, and that inhibition of calcium influx by a membrane-delimited action of a G-protein may account for L-AP4-induced presynaptic inhibition.
 ...
PMID:L-AP4 inhibits calcium currents and synaptic transmission via a G-protein-coupled glutamate receptor. 131 54

Metabotropic glutamate receptor (mGluR) is highly expressed in cerebellar Purkinje cells. The purpose of this study was pharmacological and immunocytochemical characterization of the mGluR in single cerebellar neurons, especially Purkinje cells. Ca2+ imaging with fura-2 in cultured cerebellar neurons, identified immunocytochemically, was used to record the direct effects of drugs in stable conditions. In addition, the expression of mGluR was examined, and expression of the intracellular receptor for inositol trisphosphate (IP3) produced by mGluR activation was studied immunocytochemically with specific antibodies. Purkinje neurons and some other neurons showed Ca(2+)-mobilizing responses to mGluR agonists. These responses were mediated by mGluR because they were not blocked by ionotropic GluR antagonists, were independent of the caffeine-sensitive Ca2+ pool, and were blocked by inhibitors of IP3-induced Ca2+ release. This is the first pharmacological characterization of mGluR at single Purkinje cells. The results differed as follows from those in earlier studies in which phosphoinositide turnover of the entire population of cerebellar cells was monitored: (1) the mGluR responses were not blocked by pertussis toxin or D,L-2-amino-3-phosphonopropionic acid; (2) glutamate was a potent agonist, whereas L-aspartate was ineffective; and (3) the dose-response relationship showed an all-or-none tendency. The metaboltropic response of Purkinje cells changed markedly during development, with a sharp peak after day 4 of culture, whereas mGluR and IP3 receptor proteins increased steadily during maturation. This apparent desensitization of mGluR was not blocked by inhibitors of protein kinase C (PKC) or ADP-ribosyltransferase. The metabotropic responses were mainly localized to the center of the somata of Purkinje cells even on day 4, whereas both receptor proteins were expressed throughout the cell. These results suggest that the function of mGluR is spatially and developmentally controlled by a posttranslational mechanism involving a mechanism other than phosphorylation by PKC or ADP-ribosylation.
 ...
PMID:Pharmacological and immunocytochemical characterization of metabotropic glutamate receptors in cultured Purkinje cells. 133 61

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)
 ...
PMID:Glutamate inhibits adenylate cyclase activity in dispersed rat hippocampal cells directly via an N-methyl-D-aspartate-like metabotropic receptor. 135 90

We have characterized a G-protein-coupled glutamate receptor in primary cultures of striatal neurons. Glutamate, quisqualate, or trans-1-aminocyclopentane-1,3-dicarboxylate inhibited by 30-40% either forskolin-stimulated cAMP production in intact cells or forskolin plus vasoactive intestinal peptide-activated adenylyl cyclase assayed in neuronal membrane preparations. These inhibitory effects were suppressed after treatment of striatal neurons with Bordetella pertussis toxin, suggesting the involvement of a heterotrimeric guanine nucleotide-binding protein (G protein) of the G(i)/G(o) subtype. The pharmacological profile of this glutamate receptor negatively coupled to adenylyl cyclase was different from that of the metabotropic Qp glutamate receptor coupled to phospholipase C in striatal neurons and from that of the recently cloned "mGluR2" glutamate receptor, which is negatively coupled to adenylyl cyclase when expressed in non-neuronal cells.
 ...
PMID:Characterization of a metabotropic glutamate receptor: direct negative coupling to adenylyl cyclase and involvement of a pertussis toxin-sensitive G protein. 135 3

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.
 ...
PMID:A metabotropic L-glutamate receptor agonist: pharmacological difference between rat central neurones and crayfish neuromuscular junctions. 136 Mar 66

The N-methyl-D-aspartate (NMDA)-sensitive subtype of glutamate receptor, which gates Ca(2+)-permeable ion channels, is known for its role in learning and memory formation, in the induction of long-term potentiation, and also in seizure activity and neurotoxicity. In primary cultures of cerebellar neurons, agonists of NMDA receptors induce a dose-dependent release of [3H]arachidonic acid ([3H]AA), which is potentiated by activation of the glycine-positive modulatory site and inhibited by NMDA receptor antagonists. NMDA receptor-induced [3H]AA release is inhibited by quinacrine and partially depends on the presence of extracellular calcium. The [3H]AA release is not sensitive, however, to pretreatment with pertussis or cholera toxin, which suggests a Ca(2+)-dependent activation of phospholipase A2 not employing G proteins. Pretreatment of cultures with the natural and semisynthetic sphingolipids GT1b and PKS 3, respectively, inhibits NMDA receptor-mediated [3H]AA release. We also demonstrated glutamate-evoked [3H]AA release from rat hippocampal slices, which is NMDA receptor mediated, calcium dependent and sensitive to quinacrine. Arachidonic acid and its metabolites have been shown to play a role as second messengers and to modulate neuronal activity. Moreover, they are thought to act as transsynaptic modulators in the mechanism of NMDA receptor-induced long-term potentiation in the hippocampus. Their role in ischemic brain pathology has also been postulated. Our experiments on cultured cerebellar granule cells, incubated in a Mg(2+)-free medium deprived of glucose and oxygen, demonstrated a time-dependent stimulation of [3H]AA release. This release was inhibited by antagonists of NMDA receptors and by quinacrine. Stimulation of NMDA-sensitive glutamate receptors and the subsequent calcium-mediated activation of phospholipase A2 may play a role in the in vivo release of arachidonic acid during brain ischemia. This hypothesis is supported by the observation that the enhanced level of thromboxane B2 in the gerbil brain after 5 min of global ischemia is reduced by the systemic application of either the NMDA antagonist MK-801 or the ganglioside GM1.
 ...
PMID:NMDA receptor-mediated arachidonic acid release in neurons: role in signal transduction and pathological aspects. 138 78

A complementary DNA encoding a G protein-coupled glutamate receptor from rat brain, GluGR, was cloned by functional expression in Xenopus oocytes. The complementary DNA encodes a protein of 1199 amino acids containing a seven-transmembrane motif, flanked by large amino- and carboxyl-terminal domains. This receptor lacks any amino acid sequence similarity with other G protein-coupled receptors, suggesting that it may be a member of a new subfamily. The presence of two introns flanking the central core suggests that GluGR may have evolved by exon shuffling. Expressed in oocytes, GluGR is activated by quisqualate greater than glutamate greater than ibotenate greater than trans-1-aminocyclopentyl-1,3-dicarboxylate, and it is inhibited by 2-amino-3-phosphonopropionate. Activation is blocked by Bordella pertussis toxin. These properties are typical of some metabotropic glutamate receptors.
 ...
PMID:Cloning, expression, and gene structure of a G protein-coupled glutamate receptor from rat brain. 165 24

A specific blocker of the postsynaptic glutamate receptors was found in the venom of the spider Nephila clavata. The toxin (JSTX) preferentially blocks quisqualate-type glutamate receptors in the crustacean neuromuscular synapse, squid giant synapse and hippocampal neurons in slice preparations. Following determination of the structure of JSTXs, a main component JSTX-3 with its analogs was chemically synthesized and used for the study of structure-activity relationships. 125I-labeled JSTX-3 and biotinylated JSTX-3 were synthesized for histochemical and biochemical studies of the glutamate receptors. The labeled JSTXs enabled visualization of the glutamate receptors in lobster muscle, rat cerebellum and hippocampus. By use of JSTX and pertussis toxin, a novel type of glutamate receptor (GluB receptor) was found in the crustacean neuromuscular synapse. While the postsynaptic glutamate receptor was blocked by JSTX, GluB receptor was insensitive to JSTX, but it was blocked by pertussis toxin, indicating involvement of inhibitory GTP-binding protein. Injection of GTP gamma S in the presynaptic axon mimicked the presynaptic glutamate potentials and caused presynaptic inhibitory action. Thus two types of biological toxins clearly separate the pre- and postsynaptic glutamate receptors.
 ...
PMID:Spider toxin and pertussis toxin differentiate post- and presynaptic glutamate receptors. 166 Sep 89

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.
 ...
PMID:Pharmacological characterization of phosphoinositide-linked glutamate receptor excitation of hippocampal neurons. 196 52

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.
 ...
PMID:Mechanism of the cardiovascular effects of GABAB receptor activation in the nucleus tractus solitarii of the rat. 196 70


1 2 3 4 5 Next >>