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)

The effects of the selective metabotropic glutamate receptor agonist 1-aminocyclopentane-trans-1,3-dicarboxylate (t-ACPD) on forskolin-stimulated cyclic AMP formation in guinea-pig cerebral cortex slices were determined. t-ACPD inhibited the accumulation of [3H]cyclic AMP by approximately 80%, with an IC50 value of 35 +/- 4 microM. The effect was reversible and stereoselective, with the 1S,3R isomer being approximately 400-fold more potent than the 1R,3S isomer. L-Glutamate (over a restricted concentration range) also partially inhibited the response to forskolin, but quisqualate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and N-methyl-D-aspartate (NMDA) were ineffective. The effect of t-ACPD was not blocked by antagonists of the phospholipase C-linked metabotropic glutamate receptor, the AMPA ionotropic glutamate receptor, or the NMDA receptor. In summary, our results indicate the presence of a glutamate receptor in guinea-pig brain that is activated selectively by t-ACPD and that is negatively linked to adenylyl cyclase.
...
PMID:Inhibition of forskolin-stimulated cyclic AMP formation by 1-aminocyclopentane-trans-1,3-dicarboxylate in guinea-pig cerebral cortical slices. 131 57

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.
...
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

This paper provides evidence that central sensitization and persistent nociception following formalin-induced tissue injury in rats is dependent on the production of protein kinase C. Persistent nociceptive behavior in rats induced by subcutaneous formalin injection was significantly reduced by intrathecal pretreatment with a phospholipase C inhibitor (neomycin), and an inhibitor of protein kinase C (W-7), and was significantly enhanced by a phorbol ester (phorbol 12-myristate 13-acetate, PMA) and a stimulator of protein kinase C (SC-10). It is expected that noxious inputs associated with tissue injury produce a release of aspartate and glutamate within the spinal dorsal horn which by acting at ionotropic (NMDA) and metabotropic excitatory amino acid receptors produce an increase in intracellular messengers such as calcium and diacylglycerol which stimulate protein kinase C.
...
PMID:Contribution of protein kinase C to central sensitization and persistent pain following tissue injury. 150 74

Glutamate (GLU) mediates its 'fast' excitatory transmitter action in the brain by directly gating cation-selective ion channels ('ionotropic' receptors). However, GLU can also activate another type of receptor, coupled to phospholipase C ('metabotropic' receptor). In hippocampal cells, stimulation of this metabotropic receptor by GLU, or by a racemic mixture of (1S-3R and 1R-3S) 1-aminocyclopentyl-1,3-dicarboxylate (ACPD), induces a slower excitation mediated by inhibition of K+ currents. We have assessed whether this slow form of metabotropic receptor excitation can contribute to the effects of synaptically released GLU in hippocampal slice cultures, by recording the responses of CA3 pyramidal cells to afferent mossy fibre stimulation. When the fast ionotropic response was blocked pharmacologically, mossy fibre stimulation produced a slow depolarizing postsynaptic potential associated with a decrease in membrane conductance, a depression of the slow after-hyperpolarization following a train of action potentials, and reduced accommodation during the action potential train. Under voltage-clamp, mossy fibre stimulation produced a slow voltage-dependent inward current which resembled that produced by application of exogenous ACPD or quisqualate (QUIS), and which was occluded by these metabotropic agonists. We therefore suggest that synaptically released GLU can induce two types of postsynaptic responses: a fast excitation through activation of ionotropic receptors and a slower excitation associated with inhibition of K+ conductances through activation of metabotropic receptors. This is analogous to the dual action of acetylcholine on ionotropic (nicotinic) and metabotropic (muscarinic) receptors.
...
PMID:Glutamate mediates a slow synaptic response in hippocampal slice cultures. 167

A detailed pharmacological characterization of the quisqualate (QA) receptor coupled to phospholipase C (Qp) was performed in striatal neurons. The experiments were carried out in the presence of the ionotropic antagonists MK-801 (1 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (30 microM), concentrations that block N-methyl-D-aspartate (NMDA) or alpha-amino-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in these cells. QA, ibotenate and trans-1-aminocyclopentyl-1,3-dicarboxylate (ACPD) evoked dose-dependent inositol phosphate formations with EC50 values of 0.3, 6.7 and 29 microM, respectively. QA and ibotenate had the same maximal effect (295.7 +/- 17.9% of basal, n = 6) whereas the efficacy of ACPD was somewhat lower (70.2 +/- 8.9% of the maximal quisqualate effect, n = 4). The QA-, ibotenate- and ACPD-induced maximal effects were not additive, and the inositol phosphate formations induced by high concentrations of L-aspartate (L-ASP), AMPA, kainate (KA) and domoate (DO) (100 microM or higher) were also not additive. The inositol phosphate responses induced by all these agonists were totally blocked by the phorbol ester phorbol 12,13-dibutyrate (PdBu), but not by atropine or prazosin suggesting that all these substances were able to stimulate the Qp excitatory amino acid receptor in striatal neurons. Of the excitatory amino acid receptor antagonists tested, only D,L-2-amino-3-phosphonopropionate (D,L-AP3) inhibited QA-induced InsP formation in a competitive manner (mean pKi = 4.45 +/- 0.43, n = 4). However, this drug was also a partial agonist of the Qp receptor since it stimulated the inositol phosphate formation. We found that D,L-AP3 also inhibited NMDA-induced calcium increase, in a competitive manner (mean pIC50 = 4.34 +/- 0.22, n = 8, and mean pKi = 3.7 +/- 0.11, n = 5). The Qp excitatory amino acid receptor in striatal neurons therefore closely resembles Qp receptors with high potency for agonists as described in striatal and retinal slices and synaptoneurosomes, and has several pharmacological differences compared to the Qp receptors which have low potency for agonists described in hippocampal and cortical slices, cerebellar granule cells, astrocytes and rat brain mRNA-injected oocytes.
...
PMID:Pharmacological characterization of the quisqualate receptor coupled to phospholipase C (Qp) in striatal neurons. 168 62

Associative stimulation of N-methyl-D-aspartate (NMDA) receptors and quisqualate ionotropic receptors (Qi) induces long-term potentiation at particular glutamatergic synapses. Release of arachidonic acid as a result of stimulation of NMDA receptors has been proposed to play a part in the establishment of long-term potentiation. But long-term plasticity events at some other glutamatergic synapses do not involve activation of NMDA receptors. Here we report that in mature striatal neurons in primary cultures, quisqualate can release arachidonic acid by associatively activating both quisqualate metabotropic receptors coupled to phospholipase C (Qp) and Qi receptors. Independent activation of these two receptor types with specific agonists did not stimulate arachidonic acid release. These results support a role for the associative activation of Qp and Qi receptors in synaptic plasticity events, including long-term potentiation at particular synapses.
...
PMID:Arachidonic acid released from striatal neurons by joint stimulation of ionotropic and metabotropic quisqualate receptors. 197 45

The effects of a novel glutamate analogue, (trans)-1-amino-cyclopentyl-1,3-dicarboxylate (ACPD), have been tested in striatal neurons in primary culture and in Xenopus oocytes injected with rat brain RNA. Both systems have been previously shown to contain well characterized metabotropic receptors coupled to phospholipase C (Qp), as well as ionotropic glutamate receptors. In striatal neurons, ACPD stimulated inositol phosphate (InsP) accumulation (EC50 = 9.7 +/- 2.5 microM; maximal effect, 184.7 +/- 11.6% of basal accumulation). This effect of ACPD was likely to be mediated by Qp receptors, because maximal ACPD and quisqualate-induced InsP formation were not additive. In contrast, the effects of ACPD and norepinephrine on InsP formation were additive. ACPD-induced InsP formation was not antagonised by antagonists of muscarinic and alpha 1-adrenergic receptors (1 microM atropine and 0.1 microM prazosin, respectively). In Xenopus oocytes, ACPD and quisqualate induced an oscillatory increase of a Ca2(+)-dependent chloride conductance, which is characteristic of the activation of phospholipase C-coupled receptors in this model. The specificity of ACPD on Qp receptors was demonstrated by testing the effect of this drug on quisqualate/kainate as well as on N-methyl-D-aspartate ionotropic receptors. In striatal neurons, the activation of quisqualate/kainate and N-methyl-D-aspartate receptors was tested by measurement of [3H]-gamma-aminobutyric acid release and by electrophysiological recordings using the patch-clamp technique. At concentrations as high as 1 mM, ACPD was inactive on these inotropic receptors, either as agonist or as antagonist. In conclusion, ACPD appeared to be a highly specific agonist of Qp receptors, with no activity on ionotropic glutamate receptors. It will be a useful drug to study the physiological properties of Qp receptors in vertebrate brains.
...
PMID:(trans)-1-amino-cyclopentyl-1,3-dicarboxylate stimulates quisqualate phosphoinositide-coupled receptors but not ionotropic glutamate receptors in striatal neurons and Xenopus oocytes. 216 27

Electrophysiological recording was used to study non-N-methyl-D-aspartate (NMDA) excitatory amino acid (EAA) receptors after injection of rat brain ribonucleic acid (RNA) in Xenopus laevis oocytes. Quisqualate (QA) induced two types of responses, a smooth one and an oscillatory one. These responses are probably mediated by the ionotropic (QAi, a cationic channel) and the metabotropic (QAp, a newly discovered receptor coupled to phospholipase C) QA receptors respectively. alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) only induced a smooth inward current suggesting that it acts only on QAi. Kainate (KA) also induced a smooth inward current, the maximal KA response being 10-fold higher than the maximal AMPA. AMPA inhibited the KA response in a dose-dependent and competitive manner. Amongst various complex hypotheses the simplest to explain these results would be that KA and AMPA both activate the same receptor-channel complex, AMPA inducing a smaller response than KA.
...
PMID:A specific quisqualate agonist inhibits kainate responses induced in Xenopus oocytes injected with rat brain RNA. 247 Nov 21

Brain astrocytes in primary culture from the rat or the mouse have been shown to possess ionotropic and metabotropic glutamatergic receptors. The activation of both types of receptors is responsible for a rise in the cytosolic concentration of calcium, while the stimulation of metabotropic receptors induces the accumulation of inositol phosphates. In the present study, it is demonstrated that in striatal astrocytes from mouse embryos, glutamate evokes a release of arachidonic acid. The nonionotropic receptors involved in this effect appeared to be pharmacologically distinct from those coupled to phospholipase C: (1) glutamate displayed different dose-response curves for the production of inositol phosphates (biphasic: EC50 = 25 and 300 microM) and the release of arachidonic acid (monophasic: EC50 = 200 microM); (2) L(+)-2-amino-4-phosphonobutyric acid (AP4) only antagonized the glutamate-evoked release of arachidonic acid without altering the production of inositol phosphates; (3) when used at a concentration of 0.1 mM, quisqualate induced a higher formation of inositol phosphates than glutamate (2 mM) while, in contrast to glutamate, it only weakly stimulated arachidonic acid release when used either at 0.1 mM or 1 mM. L(+)-2-amino-3-phosphonopropionic acid (AP3) suppressed both responses. The glutamate-evoked release of arachidonic acid seems to be oppositely regulated by protein kinases A and C. Indeed, the stimulation of adenylate cyclase by the beta-adrenergic agonist isoproterenol, vasoactive intestinal peptide, or pretreatment of striatal astrocytes with cholera toxin decreased the glutamate-evoked release of arachidonic acid. In contrast, ATP, which markedly stimulated inositol phosphate production, strongly potentiated the glutamate-evoked release of arachidonic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Glutamate-evoked release of arachidonic acid from mouse brain astrocytes. 750 79

The effect of ionotropic excitatory amino acids and potassium on the formation of inositol phosphates elicited by the metabotropic glutamate receptor agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD) was studied in mouse cerebellar granule cells. In Mg(2+)-containing buffers, NMDA (50-100 microM), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA; 10-1,000 microM), and high potassium (10-30 mM) enhanced synergistically the response to a maximally effective concentration of 500 microM trans-ACPD. Potentiation of the trans-ACPD response was blocked by higher concentrations of NMDA (> 500 microM) and potassium (> 35 mM) but not by AMPA (up to 1 mM). The potentiation by NMDA of the trans-ACPD-stimulated phosphoinositide hydrolysis was blocked by D,L-2-amino-5-phosphonopentanoic acid (APV), a competitive NMDA-receptor antagonist. Under Mg(2+)-free conditions, the accumulation of inositol phosphates in the presence of trans-ACPD alone was equal to that attained by trans-ACPD in Mg(2+)-containing buffers when costimulated with maximally enhancing concentrations of NMDA (50 microM). trans-ACPD potentiated synergistically the NMDA-evoked increases in cytosolic free-Ca2+ levels in Mg(2+)-containing but not in Mg(2+)-free solutions, and moreover did not enhance the AMPA-evoked increases in cytosolic free-Ca2+ levels. The calcium ionophore A23187 caused a dose-dependent increase in inositol phosphate accumulation but did not enhance the response stimulated by trans-ACPD alone. These results demonstrate the existence of cross talk between metabotropic and ionotropic glutamate receptors in cerebellar granule cells. The exact mechanism remains unclear but appears to involve interplay of G protein-coupled phospholipase C activation and regulated elevation of cytosolic free-Ca2+ levels. This study may provide a framework for future investigations at the cellular and molecular level that clarify the functional relevance and molecular mechanisms that are described.
...
PMID:Modulation by ionotropic excitatory amino acids and potassium of (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid-stimulated phosphoinositide hydrolysis in mouse cerebellar granule cells. 759 41


1 2 3 4 5 6 7 8 9 10 Next >>

---