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)

Miniature postsynaptic currents (mPSCs) were examined on autaptic innervation of single rat retinal ganglion cells in low density cultures. Removal of Ca2+ from bath solution or blocking of Ca2+ channels by Cd2+ had no detectable effect on mPSC frequency or amplitude. Thapsigargin, an agent for mobilization of Ca2+ from internal stores, increased mPSC frequency 3-5-fold in control, Ca2+-free or Cd2+-containing solutions. The inositol 1,4,5-triphosphate (IP3) receptor antago- nist, heparin; the phospholipase C (PLC) inhibitor, U73122; and caffeine abolished mPSC or decreased mPSCs frequency. Calcium imaging showed that cytosolic Ca2+ was increased by thapsigargin and decreased by caffeine. These data demonstrate that internal store-released Ca2+ regulated by the PLC/IP3/IP3-receptor pathway has critical contribution to generation and control of miniature release in retinal ganglion cells.
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PMID:Miniature postsynaptic currents depend on Ca2+ released from internal stores via PLC/IP3 pathway. 1144 35

We have investigated the effect of capsaicin on Ca(2+) release from the intracellular calcium stores. Intracellular calcium concentration ([Ca(2+)](i)) was measured in rat dorsal root ganglion (DRG) neurons using microfluorimetry with fura-2 indicator. Brief application of capsaicin (1 microM) elevated [Ca(2+)](i) in Ca(2+)-free solution. Capsaicin-induced [Ca(2+)](i) transient in Ca(2+)-free solution was evoked in a dose-dependent manner. Resiniferatoxin, an analogue of capsaicin, also raised [Ca(2+)](i) in Ca(2+)-free solution. Capsazepine, an antagonist of capsaicin receptor, completely blocked the capsaicin-induced [Ca(2+)](i) transient. Caffeine completely abolished capsaicin-induced [Ca(2+)](i) transient. Dantrolene sodium and ruthenium red, antagonists of the ryanodine receptor, blocked the effect of capsaicin on [Ca(2+)](i). However, capsaicin-induced [Ca(2+)](i) transient was not affected by 2-APB, a membrane-permeable IP(3) receptor antagonist. Furthermore, depletion of IP(3)-sensitive Ca(2+) stores by bradykinin and phospholipase C inhibitors, neomycin, and U-73122, did not block capsaicin-induced [Ca(2+)](i) transient. In conclusion, capsaicin increases [Ca(2+)](i) through Ca(2+) release from ryanodine-sensitive Ca(2+) stores, but not from IP(3)-sensitive Ca(2+) stores in addition to Ca(2+) entry through capsaicin-activated nonselective cation channel in rat DRG neurons.
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PMID:Effects of capsaicin on Ca(2+) release from the intracellular Ca(2+) stores in the dorsal root ganglion cells of adult rats. 1147 69

Pancreatic beta-cells from obese-hyperglycemic (ob/ob) mice are widely used for studying the mechanisms of insulin release, including its regulation by the cytoplasmic Ca2+ concentration ([Ca2+]i). In this study, we compared changes of [Ca2+]i in single beta-cells isolated from ob/ob mice with those from lean mice using dual-wavelength microfluorometry and the indicator fura-2. There were no differences in the frequency, amplitude, and half-width of the slow oscillations induced by glucose. Most beta-cells from the obese mice responded to 10 mM caffeine with transformation of the oscillations into sustained elevation of [Ca2+]i, a process counteracted by ryanodine. The beta-cells from the obese mice were characterized by ample generation of [Ca2+]i transients, which increased in number in the presence of glucagon. The transients became less frequent when leptin was added at a concentration as low as 1 nM. It is suggested that the excessive firing of [Ca2+]i transients in the ob/ob mice is owing to the absence of leptin and is mediated by activation of the phospholipase C signaling pathway.
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PMID:Pancreatic beta-cells from obese-hyperglycemic mice are characterized by excessive firing of cytoplasmic Ca2+ transients. 1157 29

The mode of action of venom from the ectoparasitic wasp Nasonia vitripennis in eliciting cell death was examined using an in vitro approach with BTI-TN-5B1-4 cells, and the cell responses were compared to those evoked by the extensively studied wasp toxin mastoparan. Wasp venom increased plasma membrane permeability to Na+, resulting in cellular swelling and death due to oncosis. When ouabain was used to disable Na+, K+-ATPases, the effects of venom were enhanced. Measurements of intracellular calcium using fluo-4 AM revealed a rearrangement and an increase in cytosolic [Ca+2]i within 30 min after exposure of BTI-TN-5B1-4 cells to venom. This venom-mediated increase in Ca+2 was apparently due to mobilization of intracellular stores since the changes occurred in the absence of extracellular Ca+2. Phospholipase C (PLC) inhibitors, neomycin and U-73122, blocked the venom-induced death temporarily (<3h), but by 24h, all venom-treated cells swelled and lysed. Pre-treatment of cells with caffeine or theophylline but not ryanodine attenuated the induction of oncosis by wasp venom. Anti-inflammatory peptide 1 (antiflammin 1) but not bromophenacyl bromide, agents that block phospholipase A2 (PLA2) activity, abolished the responsiveness of BTI-TN-5B1-4 cells to venom. These results suggest that venom initiates cell death by inducing Ca+2 release from intracellular stores probably via phospholipase C and IP3. A possible mode of action for venom from N. vitripennis requiring dual activation of PLC and PLA2 is discussed and compared to the pathways known to be activated by mastoparan.
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PMID:Venom from the ectoparasitic wasp Nasonia vitripennis increases Na+ influx and activates phospholipase C and phospholipase A2 dependent signal transduction pathways in cultured insect cells. 1160 74

Mammalian cell invasion by Trypanosoma cruzi requires the activation of signal transduction pathways that result in a Ca(2+) response both in the parasite and the host cell. By using drugs that interfere with the signalling processes, we investigated if the difference in the ability of T. cruzi isolates to invade host cells was associated with the activation of distinct signalling routes in the parasites. Experiments were performed with metacyclic trypomastigotes, the developmental forms that initiate infection in the mammalian host, using the highly invasive isolate CL and the poorly infective isolate G, which belong to distinct phylogenetic lineages. Treatment of parasites with adenylyl cyclase activator forskolin increased the infectivity of the G but not of the CL isolate towards HeLa cells. On the other hand, a specific protein tyrosine kinase inhibitor genistein reduced by approximately 75% the penetration of CL but not of G isolate into HeLa cells. In the CL but not in the G isolate, protein tyrosine kinase mediated the phosphorylation of a 175kDa protein in a manner inducible by a HeLa cell extract. Upon treatment with the phospholipase C inhibitor U73122, or with drugs such as caffeine, which affects Ca(2+) release from inositol-1,4,5-triphosphate-sensitive stores, or thapsigargin, an inhibitor of intracellular Ca(2+) transport ATPases, the infectivity of the CL but not of the G isolate diminished significantly (P<0.005). In both isolates, a combination of ionomycin plus NH(4)Cl or nigericin released Ca(2+) from acidic vacuoles containing a Ca(2+)/H(+) exchange system. This treatment reduced the infectivity of metacyclic forms of the G but not of the CL isolate. Taken together, these data suggest that, for host cell invasion, distinct signalling pathways are activated in metacyclic trypomastigotes of the two isolates, leading to Ca(2+) release from different intracellular compartments.
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PMID:Activation of distinct signal transduction pathways in Trypanosoma cruzi isolates with differential capacity to invade host cells. 1184 37

In the present study, we investigated the effect of interleukin-2 (IL-2) on the intracellular calcium in enzymatically isolated ventricular myocytes with the use of the spectrofluorometric techniques. It was shown that IL-2 (2.5 200 U/ml) depressed electrically induced Ca(2+) (i) transients of ventricular myocytes in a dose dependent manner. IL-2 (200 U/ml) did not alter the caffeine releasable pool of Ca(2+). Pretreatment with the non selective opioid antagonist naloxone (10(-8)mol/L) or a specific kappa opioid antagonist nor binaltorphimine (nor-BNI, 10(-8) mol/L) abolished the inhibitory effect of IL-2 (200 U/ml) on the Ca(2+) (i) transients of cardiomyocytes, whereas the specific delta opioid antagonist naltrindole (10(-6) mol/L) did not abolish the inhibitory effect. The effect of IL-2 (200 U/ml) was also abolished after pretreatment with pertussis toxin (PTX, 5 mg/L) as well as phospholipase C (PLC) inhibitor U73122 (5 10(-6) mol/L), but not by tyrosine kinase inhibitor genistein (10(-4) mol/L). It is concluded that the depressant effect of IL-2 on the Ca(2+) (i) transients of isolated ventricular myocytes is mainly mediated by cardiac kappa opioid receptor pathway including a PTX sensitive Gi-protein and PLC, but not by tyrosine kinase.
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PMID:[Effect of interleukin-2 on intracellular calcium transients in rat ventricular myocytes]. 1193 Feb 19

Bacterial Nod factors trigger a number of cellular responses in root hairs of compatible legume hosts, which include periodic, transient increases in cytosolic calcium levels, termed calcium spiking. We screened 13 pharmaceutical modulators of eukaryotic signal transduction for effects on Nod factor-induced calcium spiking. The purpose of this screening was 2-fold: to implicate enzymes required for Nod factor-induced calcium spiking in Medicago sp., and to identify inhibitors of calcium spiking suitable for correlating calcium spiking to other Nod factor responses to begin to understand the function of calcium spiking in Nod factor signal transduction. 2-Aminoethoxydiphenylborate, caffeine, cyclopiazonic acid (CPA), 2,5-di-(t-butyl)-1,4-hydroquinone, and U-73122 inhibit Nod factor-induced calcium spiking. CPA and U-73122 are inhibitors of plant type IIA calcium pumps and phospholipase C, respectively, and implicate the requirement for these enzymes in Nod factor-induced calcium spiking. CPA and U-73122 inhibit Nod factor-induced calcium spiking robustly at concentrations with no apparent toxicity to root hairs, making CPA and U-73122 suitable for testing whether calcium spiking is causal to subsequent Nod factor responses.
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PMID:Pharmacological analysis of nod factor-induced calcium spiking in Medicago truncatula. Evidence for the requirement of type IIA calcium pumps and phosphoinositide signaling. 1195 Sep 87

We recently reported that 5-hydroxytryptamine(2A) (5-HT(2A)) receptor activation on cultured glial cells induces glutamate release [J. Neurosci. Res. 67 (2002) 399]. Here we use C6 glioma cells to examine the role of calcium in this response. 5-Hydroxytryptamine (5-HT) increases glutamate release from C6 glioma cells, an effect blocked by low calcium conditions. The calcium ionophores ionomycin and calcimycin also released glutamate from C6 glioma cells in a Ca(2+)-dependent manner. The effect of 5-HT was reduced by the phospholipase C inhibitor U73122 (1-[6[[(17 beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione), but not its inactive enantomer U73343(1-[6[[(17 beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-2,5-pyrrolidinedione). The protein kinase C inhibitors staurosporine and calphostin C had no effect on the response to 5-HT, whereas the response was blocked by thapsigargin and caffeine. Neither the L-type calcium channel blockers, nifedipine and verapamil, nor the N-type calcium channel blocker omega-conotoxin GVIA inhibited the effect of 5-HT, whereas NiCl(2) and KCl blocked the response to 5-HT. We conclude that the 5-HT-induced efflux of glutamate from C6 glioma cells is Ca(2+)-dependent and involves, at least in part, the mobilisation of Ca(2+) from inositol (1,4,5) tris phosphate (IP(3)) sensitive intracellular stores.
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PMID:Studies on the role of calcium in the 5-HT-stimulated release of glutamate from C6 glioma cells. 1206 89

A possible role for signalling through phospholipase C in histamine-induced catecholamine secretion from bovine adrenal chromaffin cells has been investigated. Secretion evoked by histamine over 10 min was not prevented by inhibiting inositol-1,4,5-trisphosphate receptors with 2-APB, by blocking ryanodine receptors with a combination of ryanodine and caffeine, or by depleting intracellular Ca(2+) stores by pretreatment with thapsigargin. Inhibition of protein kinase C with Ro31-8220 also failed to reduce secretion. Inhibition of phospholipase C with ET-18-OCH(3) reduced both histamine- and K(+) -induced inositol phosphate responses by 70-80% without reducing their secretory responses. Stimulating phospholipase C with Pasteurella multocida toxin did not evoke secretion or enhance the secretory response to histamine. The secretory response to histamine was little affected by tetrodotoxin or by substituting extracellular Na(+) with N -methyl-d-glucamine(+) or choline(+), or by substituting external Cl(-) with nitrate(-). Blocking various K(+) channels with apamin, charybdotoxin, Ba(2+), tetraethylammonium, 4-aminopyridine, tertiapin or glibenclamide failed to reduce the ability of histamine to evoke secretion. These results indicate that histamine evokes secretion by a mechanism that does not require inositol-1,4,5-trisphosphate-mediated mobilization of stored Ca(2+), diacylglycerol-mediated activation of protein kinase C, or activation of phospholipase C. The results are consistent with histamine acting by depolarizing chromaffin cells through a phospholipase C-independent mechanism.
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PMID:Phospholipase C-mediated signalling is not required for histamine-induced catecholamine secretion from bovine chromaffin cells. 1206 24

To characterize the effect that a phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, LY294002, has on cytosolic calcium concentrations ([Ca2+]i), bovine airway smooth muscle cells (BASMC) and cultured human bronchial smooth muscle cells (HBSMC) were loaded with fura 2-AM, imaged as single cells and [Ca2+]i measured ratiometrically. LY294002 (50 microM) increased [Ca2+]i by 294+/-76 nM (P<0.01, n=13) and 230+/-31 nM (P<0.001, n=10) in BASMC and HBSMC, respectively, and increases occurred in the absence of extracellular calcium. In contrast, after pre-treatment with thapsigargin, LY294002 no longer increased [Ca2+]i. This calcium mobilization by LY294002 was associated with a significant functional effect since LY294002 also inhibited calcium transients to carbachol (45+/-23 nM), caffeine (45+/-32 nM), and histamine (20+/-22 nM), with controls of 969+/-190, 946+/-156, and 490+/-28 nM, respectively. Wortmannin, a different PI3-kinase inhibitor, neither increased [Ca2+]i nor inhibited transients. Also, LY294002 increased [Ca2+]i in the presence of wortmannin, U-73122, and xestospongin C. We concluded that LY294002 increased [Ca2+]i, at least in part, by mobilizing intracellular calcium stores and inhibited calcium transients. The effects of LY294002 on [Ca2+]i were not dependent on wortmannin-sensitive PI3-kinases, phospholipase C, or inositol trisphosphate receptors (IP3R). For BASMC and HBSMC, LY294002 has effects on calcium regulation that could be important to recognize when studying PI3-kinases.
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PMID:LY294002, but not wortmannin, increases intracellular calcium and inhibits calcium transients in bovine and human airway smooth muscle cells. 1212 60


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