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

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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 incorporation of [methyl-14C]choline into the choline-containing compounds of Ascaris suum muscle and the effects of acetylcholine and its agonists, carbachol and levamisole, on this incorporation were studied. Previous experiments reported a stimulation of phosphatidylcholine (lecithin) metabolism upon the administration of acetylcholine. Acetylcholine administered in vitro to A. suum muscle and body wall preparations resulted in a stimulation of phospholipase C activity that, in turn, produced an increased rate of hydrolysis of phosphatidylcholine to the corresponding diacylglyceride (DAG). The DAG, in turn, may act as a second messenger as it is required for the activation of an A. suum protein kinase C. Evidence presented here is in accordance with this hypothesis. The administration of cholinergics resulted in a stimulation of phosphatidylcholine turnover. Acetylcholine also stimulated isotope incorporation into glycerophosphorylcholine, presumably as a consequence of enhanced phospholipid turnover. These events appear to be associated with the ligand binding to the acetylcholine receptors of the A. suum muscle. Choline kinase activity is suggested in order to maintain the observed high ratio of phosphorylcholine to choline. Findings indicate that in the parasite's muscle phosphatidylcholine metabolism may be linked to receptor-dependent responses and subsequent signal transduction.
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PMID:Effects of cholinergic agents on the metabolism of choline in muscle from Ascaris suum. 159 77

1. Calcium currents (ICa) were measured in frog ventricular myocytes using the whole-cell patch clamp technique and a perfused pipette. The effect of internal perfusion with the hydrolysis-resistant GTP analogue, GppNHp (5'guanylylimidodiphosphate), on basal ICa and ICa stimulated with forskolin or isoprenaline was examined to gain insight into the role of G proteins in ICa regulation. 2. Without added guanine nucleotides, isoprenaline stimulated ICa approximately 14-fold with an EC50 of 0.09 microM. Forskolin stimulated ICa approximately 10-fold with an EC50 of 0.30 microM. 3. Internal 30 microM-GppNHp produced an approximately 80% decrease in ICa elevated by 0.3 microM-isoprenaline or 3 microM-forskolin. The inhibition of isoprenaline stimulation was due to a decrease in the maximal stimulation from approximately 14-fold to approximately 14-fold without a significant change in the EC50. In contrast, the reduction in forskolin stimulation was due to a 22-fold increase in the EC50 to 11.4 microM, with little change in maximal stimulation. 4. The inhibition of stimulated ICa by GppNHp is likely to be mediated by a G protein, because the effects of GppNHp are irreversible, and are blocked by excess GTP. ICa is affected similarly by GppNHp and by ACh. This suggests that GppNHp activates the same G protein that is normally activated by ACh, but activation by GppNHp occurs in the absence of agonist occupation of the muscarinic receptor. 5. The increase in the EC50 for forskolin produced by internal GppNHp was reversed by exposure to isoprenaline, which itself did not affect ICa amplitude. On average, exposure to isoprenaline in the presence of GppNHp caused an irreversible 81-fold decrease in the EC50 for forskolin to 0.14 microM. Stimulation of ICa by forskolin after internal GppNHp and exposure to isoprenaline was completely blocked by the protein kinase A inhibitor PKI(5-22). 6. These effects do not involve the phospholipase C system, because they are not mimicked by phorbol esters or internal inositol 1,4,5-trisphosphate (IP3) and are not blocked by bromophenacyl bromide or neomycin. 7. Direct effects of G proteins on ICa were not evident, because internal perfusion with PKI(5-22) completely inhibited isoprenaline- or forskolin-stimulated increases in ICa, and neither ACh nor internal GppNHp (30-500 microM) affected basal ICa or ICa elevated by internally perfused cyclic AMP. 8. These results suggest that the predominant site of action of the inhibitory G protein activated by either GppNHp or ACh is adenylyl cyclase. Furthermore, the internally perfused frog cardiomyocytes may provide a useful approach for probing the detailed interactions of G proteins, forskolin, and adenylyl cyclase in an intact cell.
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PMID:Regulation of Ca2+ current in frog ventricular cardiomyocytes by 5'-guanylylimidodiphosphate and acetylcholine. 165 25

Quantitatively, the major phospholipid in the muscle of the nematode Ascaris suum was found to be phosphatidylcholine (lecithin). Stimulation of Ascaris muscle with acetylcholine or the agonists carbachol and levamisole increased the level of phosphorylcholine, 1,2-diacylglycerides and phosphatidic acid. Increased levels of these compounds, together with the demonstration of phospholipase C activity, suggest that phospholipid hydrolysis may be associated with the ACh response of the muscle via second messenger pathways. In other tissues, diacylglycerides and phosphatidic acid have been reported to regulate protein kinase C activity. Protein kinase C activity also was demonstrated in the muscle of Ascaris. For optimal activity the kinase was dependent upon Ca2+, unsaturated 1,2-diacylglyceride and phospholipid. All of the data are in accord with the possible involvement of a second messenger system being operative in the ACh-stimulated contraction of Ascaris muscle.
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PMID:Phospholipids and protein kinase C in acetylcholine-dependent signal transduction in Ascaris suum. 176 27

1. Phorbol esters are known to inhibit phospholipase C-mediated hydrolysis of membrane phosphoinositide. This inhibition is attributed to participation of protein kinase C (PKC) in a negative-feedback control of phosphoinositide metabolism. We have tested this hypothesis by using different types of activators and inhibitors of PKC. 2. Phorbol-12,13-dibutyrate (PDB) inhibited the stimulatory effect of acetylcholine (ACh) on [3H]inositol monophosphate ([3H]IP) formation in cultured sympathetic neurons of the chick embryo and adrenal medulla of the rat. 3. Acetylcholine (ACh) and 5-hydroxytryptamine (5-HT) activated neuronal PKC by 3- to 8-fold. The extent of PKC activation by 100 microM-ACh was comparable to that of 100 nM-PDB. Activation of PKC by pre-incubation of sympathetic neurons with ACh (or 5-HT) did not inhibit the stimulatory effects of ACh (or 5-HT) on [3H]IP formation. 4. Pre-treatment of sympathetic neurons or adrenal medulla with a PKC inhibitor H7 (1-(5-isoquinolinyl-sulphonyl)-2-methyl-piperazine) almost completely blocked activation of the enzyme induced by PDB, ACh or 5-HT. However, blockade of PKC did not prevent the inhibitory effects of PDB on ACh-induced [3H]IP formation. 5. Vasoactive intestinal polypeptide (VIP) and muscarine induced catecholamine secretion from the perfused adrenal medulla via formation of inositol-1,4,5-tirisphosphate (IP3). Phorbol-12,13-dibutyrate decreased muscarine-induced catecholamine secretion. However, activation of PKC by VIP had no effect on muscarine-induced catecholamine secretion and vice versa. 6. These results suggest that PKC is not negatively coupled to phosphoinositide hydrolysis in sympathetic neurons and chromaffin cells. Phorbol esters must have targets other than PKC to interfere with the phosphoinositide hydrolysis.
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PMID:Phosphoinositide hydrolysis is not negatively regulated by protein kinase C in the peripheral tissues of rat and chick. 217 Jun 29

Acetylcholine (ACh)-activated channel properties were examined on an aneural culture of chick embryo myotubes by using patch-clamp techniques. Changes in conductance, open time and closed time were induced by the selective activator of the calcium- and phospholipid-dependent C-kinase (PKc), 12-O-tetradecanoylphorbol-13-acetate (TPA). The action of TPA was mimicked by exogenous phospholipase C and was blocked by the PKc inhibitor, 1-(5-isoquinolinylsulphonyl)-2-methyl-piperazine. In addition to its gating action, ACh was shown to stimulate phosphoinositide turnover and to translocate PKc from the cytosol to the cell membrane. Both these ACh-induced effects were inhibited by curare and not substantially affected by atropine. Bath-applied ACh outside the patch-pipette in the cell-attached patch-clamp mode, had a strong effect on the ACh-activated channels in the patch membrane, in a way that resembled the action of TPA. These findings raise the possibility that ACh regulates its own nicotinic receptors through the C-kinase system.
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PMID:Acetylcholine may regulate its own nicotinic receptor-channel through the C-kinase system. 288 74

A factor (Substance B) has been isolated from brain which reverses the presynaptically-modulated inhibition of evoked ACh release from both guinea-pig myenteric plexus-longitudinal muscle synaptosomes and the intact strip. Inhibitory modulating agents whose activity is reversed by Substance B include oxotremorine, 2-chloroadenosine, clonidine, and morphine. In addition to brain, Substance B is also present in heart and ileum but not in liver or kidney. As determined by Biogel P2 chromatography, this factor appears to have a molecular weight of around 700. It is not destroyed by preincubation with periodate, amylase, adenosine deaminase, pronase, trypsin, phospholipase C or carboxypeptidase Y.
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PMID:Isolation of a factor that reverses presynaptic inhibition of acetylcholine release. 357 23

We have studied putative nicotinic acetylcholine receptors in the optic lobe of the newborn chick, using 125I-labeled alpha-bungarotoxin, a specific blocker of acetylcholine receptors in the neuromuscular junction, and [3H]acetylcholine, a ligand which in the presence of atropine selectively labels binding sites of nicotinic character in rat brain cortex (Schwartz et al., 1982). [3H]Acetylcholine binds reversibly to a single class of high affinity binding sites (KD = 2.2 X 10(-8) M) which occur at a tissue concentration of 5.7 pmol/g. A large fraction (approximately 60%) of these binding sites is solubilized by Triton X-100, sodium cholate, or the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate. Solubilization increases the affinity for acetylcholine and several nicotinic drugs from 1.5- to 7-fold. The acetylcholine-binding macromolecule resembles the receptor for alpha-bungarotoxin present in the same tissue with respect to subcellular distribution, hydrodynamic properties, lectin binding, and agonist affinity rank order. It differs from the toxin receptor in affinity for nicotinic antagonists, sensitivity to thermal inactivation, and regional distribution. The solubilized [3H]acetylcholine binding activity is separated from the toxin receptor by incubation with agarose-linked acetylcholine, by affinity chromatography on immobilized Naja naja siamensis alpha-toxin, and by precipitation with a monoclonal antibody to chick optic lobe toxin receptor.
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PMID:Biochemical characterization of two nicotinic receptors from the optic lobe of the chick. 405 85

1. A study was made of the effects of phospholipase C (PhC) on the resting membrane potential, input resistance, action potential and acetylcholine sensitivity of innervated and chronically denervated single muscle fibres of the rat.2. In doses higher than 1.5 mug/ml. PhC significantly increased the ionic permeability of the muscle membrane (indicated by a fall in input resistance) and reduced the resting membrane potential of innervated fibres. The ;fast' or ;white' extensor digitorum longus muscle was the most sensitive and the ;slow' or ;red' soleus the least sensitive muscle. A similar difference was observed among ;fast' and ;slow' muscles of the chicken, the posterior latissimus dorsi being far more sensitive than the ;slow' anterior latissimus dorsi muscle. Chronically denervated muscles were more resistant to these actions of PhC than innervated ones but even after denervation the ;fast' muscles remained more sensitive than the ;slow' muscles.3. The action-potential generating mechanism in the ;fast' and ;slow' muscle was completely and irreversibly blocked by 1.5 mug/ml. of PhC within 1 hr. Furthermore the innervated and chronically denervated muscles were equally sensitive to this effect of PhC. The enzyme caused a gradual increase in the threshold for excitation, reduction in the rate of rise and the amplitude of the action potential. The input resistance and the resting membrane potential were not reduced by this dose of PhC.4. Acetylcholine sensitivity of chronically denervated muscles was not affected by PhC in doses that abolished the electrical excitability of the membrane. When PhC reduced the input resistance and the resting membrane potential a decrease was also observed in the response to applied acetylcholine.5. The results suggest that PhC by acting at the polar heads of membrane phospholipids interferes with the ionic carrier mechanism which generates the action potential. The differences in sensitivity between ;fast' and ;slow' muscles and between innervated and chronically denervated ones are tentatively explained on the basis of heterologous membrane phospholipids and/or variations in their stereochemical arrangement.
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PMID:Influence of phospholipase C on some electrical properties of the skeletal muscle membrane. 603 15

Acetylcholine receptors were purified to homogeneity from chicken embryonic, adult innervated and denervated muscles, by bio-specific chromatographies using immobilised alpha-neurotoxin and lentil lectin. A minimum specific activity for the pure receptor was estimated to be 6000 nmol alpha-toxin binding sites/g protein. For analysis, the receptors were radio-iodinated or tritiated to high specific radioactivity with succinimidyl-[2,3-3H]propionate. All of the iodinated protein present in the purified receptor preparation reacted with antibody against the pure acetylcholine receptor from Torpedo marmorata electric organ. In the case of all three muscle types used the same oligomeric forms were obtained. The principal form has a sedimentation coefficient of about 9 S, while a minor species (approximately 5S) was also appreciable in crude preparations of embryonic and denervated muscles. Immunization of rabbits with the homogenous receptor from chicken denervated muscle produced muscle weakness characteristic of experimental autoimmune myasthenia gravis. These antisera were equally reactive towards the receptor --125I-alpha-bungarotoxin complexes from chick innervated and denervated muscles. Likewise, the electrophoretic mobilities of the receptors (9-S form) from all three muscle types were identical, as were the isoelectric points of their complexes with 125I-alpha-bungarotoxin. Collectively, these findings and associated ones on subunit structure denote that the 9-S receptor molecules from junctional and extra-junctional area and embryonic stage of chicken muscle are indistinguishable by all criteria yet applied to them.
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PMID:Similarity of acetylcholine receptors of denervated, innervated and embryonic chicken muscles. 1. Molecular species and their purification. 714 Jul 38

We have developed the coexpression system of both delta-opioid receptor (DOR1) and M2-muscarinic receptor (M2) which mediate agonist-evoked currents due to common post-receptor mechanisms including Gi1 and phospholipase C (PLC) activation in Xenopus oocytes reconstituted with Gi1 alpha. The DOR1-currents by 100 nM D-Ser2-leu-enkephalin-Thr6 (DSLET) were selectively desensitized by 10 nM phorbol 12-myristate 13-acetate (PMA). The PMA-desensitization of DSLET-currents was abolished in the presence of calphostin C, a protein kinase C inhibitor, or reversed by an intracellular injection of calcineurin, a protein phosphatase 2B. When a higher concentration (3 microM) of DSLET was used, DSLET-currents were rapidly desensitized by repeated challenges of DSLET itself. However, repeated challenges of 10 microM ACh caused no influence on such DSLET- or M2-currents. The desensitization of DSLET-currents was selectively reversed by protein kinase C inhibitors. Similar results were also obtained with various delta-opioid agonists. These results suggest that protein kinase C is involved in the homologous desensitization of delta-opioid receptors.
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PMID:Protein kinase C involvement in homologous desensitization of delta-opioid receptor coupled to Gi1-phospholipase C activation in Xenopus oocytes. 747


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