Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The N-methyl-D-aspartate (NMDA) receptor of rat cerebellar granule cells in primary culture is inhibited by phospholipase C-coupled receptor activation. In the absence of ionotropic agonist, cells modulate their cytoplasmic free Ca2+, [Ca2+]c, in response to stimulation of M3 muscarinic receptors, metabotropic glutamate receptors, and endothelin receptors by the respective agonists carbachol, trans-1-amino-1,3-cyclopentanedicarboxylic acid, and endothelin-1. The response is consistent with the ability of phospholipase C-coupled receptors to release a pool of intracellular Ca2+ and induce a subsequent Ca2+ entry into the cell; both of these responses can be abolished by discharge of internal Ca2+ stores with low concentrations of ionomycin or thapsigargin. In the case of cells stimulated with NMDA, the [Ca2+]c response to the phospholipase C-coupled agonists is complex and agonist dependent; however, in the presence of ionomycin each agonist produces a partial inhibition of the NMDA component of the [Ca2+]c signal. This inhibition can be mimicked by the protein kinase C activator 4 beta-phorbol 12,13-dibutyrate. It is concluded that NMDA receptors on cerebellar granule cells are inhibited by phospholipase C-coupled muscarinic M3, glutamatergic, and endothelin receptors via activation of protein kinase C.
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PMID:Interactions between phospholipase C-coupled and N-methyl-D-aspartate receptors in cultured cerebellar granule cells: protein kinase C mediated inhibition of N-methyl-D-aspartate responses. 138 23

The amyloid beta protein (25-35) stimulated appearance of 3H-inositol phosphates from [3H]inositol-prelabeled LA-N-2 cells was investigated. This stimulation was unaltered by extra- and intracellular calcium chelators in a calcium-free medium or by several protein kinase inhibitors. This phospholipase C stimulation by amyloid beta protein appeared to be pertussis toxin sensitive. It is possible that this phospholipase C stimulation by amyloid beta protein is a receptor-mediated process. This possibility is based on two related observations. The stimulation is ablated by the presence of conventional antagonists for metabotropic, adrenergic, and bombesin agonists. The IC50 values were 12 microM for propranolol, 15 microM for AP-3, and 25 nM for [Tyr4,D-Phe12]bombesin. Additional support comes from results of desensitization and resensitization experiments. Amyloid beta protein stimulation of phospholipase C was absent from LA-N-2 cells previously treated with norepinephrine, trans-1-amino-1,3-cyclopentanedicarboxylic acid (t-ACPD), bombesin, or amyloid beta peptide. In a similar manner, LA-N-2 cells previously treated with amyloid beta protein were no longer responsive to norepinephrine, t-ACPD, or bombesin. The responsiveness to amyloid beta protein returned, subsequent to a period of resensitization for the individual agonists. It is suggested that this observed amyloid beta protein stimulation of phospholipase C may be responsible for the elevated quantity of inositol seen in the brains of Alzheimer's disease patients.
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PMID:Amyloid beta protein (25-35) stimulation of phospholipase C in LA-N-2 cells. 920 17

To examine the effects of glutamatergic neurotransmission on amyloid processing, we stably expressed the metabotropic glutamate receptor subtype 1alpha (mGlu-R1alpha) in HEK 293 cells. Both glutamate and the selective metabotropic agonist 1-amino-1,3-cyclopentanedicarboxylic acid (ACPD) rapidly increased phosphatidylinositol (PI) turnover four- to fivefold compared with control cells that were transfected with the expression vector alone. Increased PI turnover was effectively blocked by the metabotropic antagonist alpha-methyl-4-carbophenylglycine (MCPG), indicating that heterologous expression of mGluR1alpha resulted in efficient coupling of the receptors to G protein and phospholipase C activation. Stimulation of mGluR1alpha with glutamate, quisqualate, or ACPD rapidly increased secretion of the APP ectodomain (APPs); these effects were blocked by MCPG. The metabotropic receptors were coupled to APP processing by protein kinases and by phospholipase A2 (PLA2), and melittin, a peptide that stimulates PLA2, potently increased APPs secretion. These data indicate that mGluR1alpha can be involved in the regulation of APP processing. Together with previous findings that muscarinic and serotonergic receptor subtypes can increase the secretion of the APP ectodomain, these observations support the concept that proteolytic processing of APP is under the control of several major neurotransmitters.
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PMID:Metabotropic glutamate receptor subtype mGluR1alpha stimulates the secretion of the amyloid beta-protein precursor ectodomain. 923 30

Our previous studies using an in vitro model of traumatic injury have shown that stretch injury of astrocytes causes a rapid elevation in intracellular free calcium ([Ca2+]i), which returns to near normal by 15 min postinjury. We have also shown that after injury astrocyte intracellular calcium stores are no longer able to release Ca2+ in response to signal transduction events mediated by the second messenger inositol (1,4,5)-trisphosphate (IP3, Rzigalinski et al., 1998). Therefore, we tested the hypothesis that in vitro injury perturbs astrocyte IP3 levels. Astrocytes grown on Silastic membranes were labeled with [3H]-myo-inositol and stretch-injured. Cells and media were acid-extracted and inositol phosphates isolated using anion-exchange columns. After injury, inositol polyphosphate (IPx) levels increased up to 10-fold over uninjured controls. Significant injury-induced increases were seen at 5, 15, and 30 min and at 24 and 48 h postinjury. Injury-induced increases in IPx were equivalent to the maximal glutamate and trans-(1S,3R)-1-amino-1,3-cyclopentanedicarboxylic acid-stimulated IPx production, however injury-induced increases in IPx were sustained through 24 and 48 h postinjury. Injury-induced increases in IPx were attenuated by pretreatment with the phospholipase C inhibitors neomycin (100 microM) or U73122 (1.0 microM). Since we have previously shown that astrocyte [Ca2+]i returns to near basal levels by 15 min postinjury, the current results suggest that IP3-mediated signaling is uncoupled from its target, the intracellular Ca2+ store. Uncoupling of IP3-mediated signaling may contribute to the pathological alterations seen after traumatic brain injury.
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PMID:Traumatic injury of cultured astrocytes alters inositol (1,4,5)-trisphosphate-mediated signaling. 1116 88