Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.4.3 (phospholipase C)
18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Neuronal plasticity has been suggested to be the physical substrate for changes underlying the expression of memory. One model which has attracted wide attention as a possible candidate of such neuronal plasticity is long-term potentiation (LTP), mainly investigated in the hippocampus of rodents. Moreover, various processes with different time constants may underlie LTP, and these phases show striking correspondence to different phases of memory. 2. Pharmacological evidence strongly implicates that the neurotransmitter glutamate plays a major role in LTP. Although the involvement of ionotropic glutamate receptors has been proven, the role of the newly discovered metabotropic glutamate receptors is still uncertain. 3. Metabotropic glutamate receptors (mGluRs) comprise a whole family with currently eight members grouped into three classes according to their amino acid sequence identity and pharmacological profile. They are G-protein coupled, either positively linked to phospholipase C (class I) or negatively linked to adenylate cyclase (class II and III), and among other effects are known to induce phosphorylation of ionotropic glutamate receptors as well as modulate the excitability of neurons. Finally, they are heterogeneously distributed throughout the brain. 4. In hippocampal slice preparations, mGluRs have been shown to be involved in the induction of LTP in CA1 and dentate gyrus by some investigators, but others have failed to reproduce such experiments, leaving the question: what are the appropriate conditions for mGluR-mediated LTP? 5. In vivo, metabotropic receptor antagonists have been shown to block, and agonists to facilitate, induction and maintenance of LTP, mainly at perforant path/dentate granule cell synapses. As demonstrated in behavioral investigations, mGluRs apparently play an important part in hippocampus-dependent learning paradigms. As in LTP, antagonists block memory formation; in contrast to LTP, agonists also prevent memory formation. In memory recall metabotropic receptors seem to play no role. 6. Based on current information the authors develop models for a role of mGluRs in both LTP and memory formation. Activation of metabotropic receptors plays a particular modulatory role when high frequency stimulation is weak. Strong tetanization may bypass mGluRs by stimulating other systems leading to, at least phenomenologically, similar LTP, Behaviorally, mGluRs possibly set the signal to noise ratio of the hippocampal circuit.
...
PMID:Comparing the role of metabotropic glutamate receptors in long-term potentiation and in learning and memory. 887 63

Activation of phospholipase C (PLC) increases intracellular Ca2+ and may play a role in delayed neuronal death after ischemia. Because changes in intracellular Ca2+ are believed to participate in ischemic neuronal injury, we tested the hypothesis that PLC beta protein levels are temporally altered in brain regions that undergo neurodegeneration after global incomplete ischemia. Dogs (n = 12) were subjected to 20 minutes of global incomplete ischemia followed by recovery of either 1 (n = 5) or 7 days (n = 7). Six sham-operated animals were used as nonischemic controls. In hematoxylin and eosin-stained brain sections, neuronal density at 1 day after ischemia was unchanged relative to nonischemic controls in hippocampus CA1, caudate, and cerebellar cortex (anterior lobule). However, at 7 days after ischemia, neuronal densities were decreased to 56 +/- 15% (mean +/- SD) and 75 +/- 17% of control in CA1 and caudate, respectively. At 1 and 7 days after ischemia, the percentage of neurons showing ischemic injury increased from 13 +/- 10 to 40 +/- 35% in CA1, 24 +/- 25 to 59 +/- 16% in cerebellum, and 4 +/- 2 to 18 +/- 12% in caudate. Densitometric analysis of immunocytochemically stained brain sections from controls (n = 3). 1 day after ischemia (n = 3), and 7 days after ischemia (n = 5) revealed that PLC beta immunoreactivity was increased in cerebellum at 1 day (0.274 +/- 0.013 v 0.295 +/- 0.005 optical density units [OD] in control and 1 day, respectively) and 7 days (0.108 +/- 0.009 v 0.116 +/- 0.005 O.D. in control and 7 days, respectively). PLC beta immunoreactivity was unchanged after ischemia in caudate and hippocampus. Western blot analysis of PLC beta immunoreactivity in the cerebellar cortex and hippocampus in the control (n = 3), 1 day (n = 2), and 7 days after ischemia (n = 2) groups showed that PLC beta levels were increased after ischemia in cerebellum 266% and 227% above control at 1 and 7 days, respectively. However, in hippocampus, PLC expression after ischemia was unchanged at 97% and 84% of control at 1 and 7 days, respectively. These results show that delayed neuronal degeneration after global incomplete ischemia is accompanied by regional abnormalities in PLC levels. Elevated PLC levels early may represent an aberrant signal transduction mechanism resulting in delayed cell damage, whereas decreased PLC levels later after ischemia may reflect ongoing neurodegeneration.
...
PMID:Delayed neuronal death after global incomplete ischemia in dogs is accompanied by changes in phospholipase C protein expression. 918 90

Cannabinoid receptors are molecular targets for marijuana and hashish, the widespread drugs of abuse. These receptors are expressed in areas of the central nervous system that contribute in important ways to the control of memory, cognition, movement and pain perception. Indeed, such functions can be strongly influenced by cannabinoid drugs, with consequences that include euphoria, analgesia, sedation and memory impairment. Although the pharmacology of cannabinoid drugs is now beginning to be understood, we still lack essential information on the endogenous signalling system(s) by which cannabinoid receptors are normally engaged. An endogenous ligand for cannabinoid receptors, anandamide, has been described. Here we report that sn-2 arachidonylglycerol (2-AG), a cannabinoid ligand isolated from intestinal tissue, is present in brain in amounts 170 times greater than anandamide. 2-AG is produced in hippocampal slices by stimulation of the Schaffer collaterals, an excitatory fibre tract that projects from CA3 to CA1 neurons. Formation of 2-AG is calcium dependent and is mediated by the enzymes phospholipase C and diacylglycerol lipase. 2-AG activates neuronal cannabinoid receptors as a full agonist, and prevents the induction of long-term potentiation at CA3-CA1 synapses. Our results indicate that 2-AG is a second endogenous cannabinoid ligand in the central nervous system.
...
PMID:A second endogenous cannabinoid that modulates long-term potentiation. 928 89

Metabotropic glutamate receptors (mGluRs) couple to heterotrimeric G-proteins and regulate cell excitability and synaptic transmission in the CNS. Considerable effort has been focused on understanding the cellular and biochemical mechanisms that underlie regulation of signaling by G-proteins and their linked receptors, including the mGluRs. Recent findings demonstrate that regulators of G-protein signaling (RGS) proteins act as effector antagonists and GTPase-activating proteins for Galpha subunits to inhibit cellular responses by G-protein-coupled receptors. RGS4 blocks Gq activation of phospholipase Cbeta and is expressed broadly in rat brain. The group I mGluRs (mGluRs 1 and 5) couple to Gq pathways to regulate several effectors in the CNS. We examined the capacity of RGS4 to regulate group I mGluR responses. In Xenopus oocytes, purified RGS4 virtually abolishes the mGluR1a- and mGluR5a-mediated but not the inositol trisphospate-mediated activation of a calcium-dependent chloride current. Additionally, RGS4 markedly attenuates the mGluR5-mediated inhibition of potassium currents in hippocampal CA1 neurons. This inhibition is dose-dependent and occurs at concentrations that are virtually identical to those required for inhibition of phospholipase C activity in NG108-15 membranes and reconstituted systems using purified proteins. These findings demonstrate that RGS4 can modulate mGluR responses in neurons, and they highlight a previously unknown mechanism for regulation of G-protein-coupled receptor signaling in the CNS.
...
PMID:RGS4 inhibits signaling by group I metabotropic glutamate receptors. 943 12

Activation of metabotropic glutamate receptors (mGluRs) with 1-aminocyclopentane-1S,3R-dicarboxylic acid 20 min prior to tetanus facilitates, or "primes," subsequent induction of long-term potentiation (LTP; Cohen and Abraham, J Neurophysiol 1996;76:953-962). In the present study, we investigated the receptor specificity and associated second messenger pathways involved in the mGluR priming effect by using field potentials recorded from area CA1 of rat hippocampal slices. In controls, mild theta-burst or high-frequency (100 Hz) stimulation induced 16% and 21% LTP, respectively. A 10-min application of the group I mGluR agonist 3,5-dihydroxyphenylglycine (DHPG) caused a transient depression of synaptic responses but a significant enhancement of subsequent LTP for both tetanus protocols (45% and 41% LTP, respectively). Maximal LTP, induced by stronger tetanization protocols, was not enhanced by DHPG, nor was mild LTP facilitated by post-tetanic application of DHPG. Priming with agonists selective for group II or III mGluRs had no effect on LTP. The mGluR antagonists L-2-amino-3-phosphonopropionic acid and 1-aminoindan-1,5-dicarboxylic acid inhibited the LTP facilitatory effect of DHPG but not the transient response depression, whereas alpha-methyl-4-carboxyphenylglycine produced the opposite effects. Priming with N-methyl-D-aspartate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid did not facilitate LTP induction. Prior activation of muscarinic acetylcholine receptors produced at best a weak priming effect. Inhibition of phospholipase C by U-73122 completely abolished the priming of LTP by DHPG. We conclude that mGluR priming of LTP results from biochemical cascades triggered by activation of phospholipase C coupled to group I mGluRs.
...
PMID:Priming of long-term potentiation induced by activation of metabotropic glutamate receptors coupled to phospholipase C. 957 22

1. During block of gamma-aminobutyric acid-A-mediated inhibition, low-frequency stimulation (2 Hz, 900 pulses) to Schaffer collateral-CA1 neuron synapses of adult rat hippocampus induced an N-methyl-D-aspartate receptor-independent, postsynaptic Ca2+-dependent depression of synaptic strength (long-term depression; LTD). 2. Ratio imaging with fura-2 revealed moderate dendritic [Ca2+] increases (approximately 500 nM) during only the initial approximately 30 s of the 7.5 min stimulation period. Conditioning for 30 s was, however, insufficient to induce LTD. 3. The [Ca2+] changes were insensitive to the metabotropic glutamate receptor (mGluR) antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG). MCPG, however, completely blocked LTD when present during conditioning. 4. The [Ca2+] changes were abolished by postsynaptic hyperpolarization (-110 mV at the soma). Hyperpolarizing neurons to -110 mV during conditioning significantly attenuated LTD induction. 5. LTD induction was also blocked by the postsynaptic presence of the protein kinase C inhibitor peptide PKC(19-36). 6. These results suggest that LTD induction in adult hippocampus by prolonged low-frequency stimulation depends on both a rapid Ca2+ influx through voltage-sensitive channels and synaptic stimulation of mGluRs which may be coupled to phospholipase C.
...
PMID:Requirement of rapid Ca2+ entry and synaptic activation of metabotropic glutamate receptors for the induction of long-term depression in adult rat hippocampus. 971 58

The necessity for phospholipase C (PLC), the enzyme which produces the second messenger molecules inositol trisphosphate (IP3) and diacylglycerol, for the induction of long-term depression (LTD) was tested at Schaffer collateral-CA1 synapses in hippocampal slices in vitro. We report here that bath application of a selective cell-permeant PLC inhibitor, U-73122 (10 microM), does block the induction of LTD. In contrast, neither the inactive analog U-73343 (10 microM), nor application of U-73122 during the maintenance phase of LTD, impaired expression of LTD. Furthermore, postsynaptic infusion of U-73122 (100 microM) into single CA1 pyramidal neurons also prevented the induction of LTD. Since mGluR5 is the only metabotropic glutamate receptor subtype coupled to inositide turnover in field CA1, we conclude that the postsynaptic calcium store necessary for the induction of homosynaptic LTD is gated by IP3, through activation of mGluR5 coupled to phospholipase C.
...
PMID:Postsynaptic phospholipase C activity is required for the induction of homosynaptic long-term depression in rat hippocampus. 973 84

Quisqualate is a potent specific agonist for Group 1 metabotropic glutamate receptors (mGluR's), that activate G protein-coupled phospholipase C (PLC) in a molecular signal-transduction mechanism that raises cytoplasmic Ca2+ and, when excessive, damages hippocampal neurons. Psychosine (beta-galactosylsphingosine), a cationic lysosphingolipid occurring naturally in nervous tissues, dose-dependently inhibited PLC activation induced by metabotropic alpha 1-adrenergic receptor signaling in cultured rat brain astrocytes in vitro. In the present study, we have tested neuroprotective efficacy of psychosine in vivo, in a rat model of glutamate excitotoxicity induced by intracerebroventricular (i.c.v.) administration of quisqualate. A sublethal i.c.v. dose of quisqualate caused episodes of prolonged akinesia and convulsions, and major damage to pyramidal neurons of the hippocampal CA1 and CA3 sector, but not to granule cell neurons of the dentate gyrus. Prior infusion of psychosine greatly attenuated quisqualate-induced behaviors, and fully prevented destruction by quisqualate of vulnerable hippocampal neurons. Psychosine may prove useful in prophylaxis of neurodegenerative disorders that arise from intensive hippocampal Group 1 mGluR stimulation.
...
PMID:Psychosine blocks quisqualate-induced glutamate excitotoxicity in hippocampal CA sector neurons. 974 72

Alternative splicing has been shown to occur at the metabotropic glutamate receptor 1 (mGluR1) gene. Three main isoforms that differ in their carboxy-termini have been described so far and named mGluR1alpha, mGluR1beta and mGluR1c. These variants when expressed in recombinant systems all activate phospholipase C, although the [Ca2+] signals generated have different kinetics. Tissue distribution studies of specific mGluR1 splice variants are limited to the mGluR1alpha isoform. In the present work, we examined the localization of mGluR1beta in the adult rat and mouse forebrain by using a specific antipeptide antibody. Furthermore, the mGluR1beta immunostaining was compared with that obtained with antibodies specific for mGluR1alpha or with a pan-mGluR1 antibody which recognizes all isoforms. mGluR1beta-like immunoreactivity (LI) was found confined to the neuropil and neuronal perikarya and appeared discretely distributed in the rodent forebrain. Differential cellular distribution between mGluR1alpha and mGluR1beta was observed. In the hippocampus, mGluR1alpha-LI was restricted to non-principal neurons in all fields, whereas mGluR1beta-LI was strongest in principal cells of the CA3 field and dentate granule cells but absent in CA1. We have also shown that the vast majority of neurons in the striatum express mGluR1. The predominant form appeared to be mGluR1beta, with a distribution pattern reflecting the patch-matrix organization of the striatum. The specificity of the immunoreactivity described for mGluR1 splice variants was confirmed in mGluR1-deficient mice. The observation of a different cellular and regional distribution of mGluR1 splice variants, in particular in the hippocampus, suggests that they may mediate different roles in synaptic transmission.
...
PMID:Immunohistochemical localization of the mGluR1beta metabotropic glutamate receptor in the adult rodent forebrain: evidence for a differential distribution of mGluR1 splice variants. 977 43

1. Whole-cell patch-clamp recordings were made from visually identified hippocampal interneurones in slices of rat brain tissue in vitro. Bath application of the bombesin-like neuropeptides gastrin-releasing peptide (GRP) or neuromedin B (NMB) produced a large membrane depolarization that was blocked by pre-incubation with the subtype 2 bombesin (BB2) receptor antagonist [D-Phe6, Des-Met14]bombesin-(6-14)ethyl amide. 2. The inward current elicited by NMB or GRP was unaffected by K+ channel blockade with external Ba2+ or by replacement of potassium gluconate in the electrode solution with caesium acetate. 3. Replacement of external NaCl with Tris-HCl significantly reduced the magnitude of the GRP-induced current at -60 mV. In contrast, replacement of external NaCl with LiCl had no effect on the magnitude of this current. 4. Photorelease of caged GTPgammaS inside neurones irreversibly potentiated the GRP-induced current at -60 mV. Similarly, bath application of the phospholipase C (PLC) inhibitor U-73122 significantly reduced the size of the inward current induced by GRP. 5. Reverse transcription followed by the polymerase chain reaction using cytoplasm from single hippocampal interneurones demonstrated the expression of BB2 receptor mRNA together with glutamate decarboxylase (GAD67). 6. Although bath application of GRP or NMB had little or no effect on the resting membrane properties of CA1 pyramidal cells per se, these neuropeptides produced a dramatic increase in the number and amplitude of miniature inhibitory postsynaptic currents in these cells in a TTX-sensitive manner.
...
PMID:Bombesin-like peptides depolarize rat hippocampal interneurones through interaction with subtype 2 bombesin receptors. 1042 15


<< Previous 1 2 3 4 5 6 7 Next >>

---