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 I1-imidazoline receptor is expressed in the rostral ventrolateral medulla (RVLM) where it mediates vasodepression, and in PC12 pheochromocytoma cells where it elicits generation of diacylglycerol independent of phosphatidylinositol turnover or activation of phospholipase D. We hypothesized that the I1-imidazoline receptor couples to a phosphatidylcholine-selective phospholipase C (PC-PLC). The I1-agonist moxonidine elicited diacyglyceride accumulation and release of [3H]phosphocholine from PC12 cells prelabeled with [3H]choline. The PC-PLC inhibitor D609 abolished both responses. Microinjection of D609 into the RVLM of hypertensive rats blocked the vasodepressor response to intravenous moxonidine. These data implicate PC-PLC in cellular and organismic responses to I1-receptor stimulation.
...
PMID:Activation of phosphatidylcholine-selective phospholipase C by I1-imidazoline receptors in PC12 cells and rostral ventrolateral medulla. 913 34

Rat PC 12 pheochromocytoma cells lack alpha2-adrenergic receptors but express plasma membrane I1-imidazoline receptors. In response to the I1-agonist moxonidine, diglycerides are generated via phosphatidylcholine-selective phospholipase C, and prostaglandin E2 is released. This report characterizes I-receptor-mediated release of arachidonic acid, the precursor to the prostaglandins. PC12 cells were incubated with [3H]arachidonic acid for 24 h and superfused with 0.01% bovine serum albumin in Krebs' physiological buffer at 1 ml/min. Calcium ionophore increased arachidonic acid release only marginally, implying that in PC12 cells arachidonic acid release is not driven by calcium. The I1-agonist moxonidine at concentrations between 10 nM and 1.0 microM rapidly elicited up to two-fold increases in [3H]arachidonic acid release. Guanabenz, a potent alpha2-agonist and I2-ligand, had no effect. The selective I1-antagonist efaroxan blocked the action of moxonidine. The phospholipase A2 inhibitor aristolochic acid had no effect, suggesting that arachidonic acid release may be through an indirect pathway, possibly involving diglycerides. Thus, I1-imidazoline receptors in PC12 cells are coupled to arachidonic acid release through an as yet unknown pathway.
...
PMID:Arachidonic acid release from PC12 pheochromocytoma cells is regulated by I1-imidazoline receptors. 985 63

Nerve growth factor differentiates precursor cells into sympathetic neurons. Does acquisition of a "neuronal" phenotype after nerve growth factor involve biosynthesis of chromogranin A, the major soluble protein in chromaffin granule cores? Nerve growth factor activated chromogranin A gene expression 7.6-fold in PC12 pheochromocytoma cells, and similarly activated PC12-transfected mouse, rat or human chromogranin A promoter/reporter constructs. Chromogranin A promoter 5'-deletions narrowed the nerve growth factor response element to a region from - 77 to - 61 bp upstream of the cap site, a region containing the chromogranin A cyclic AMP response element (TGACGTAA). Three different site-directed mutations of the cyclic AMP response element each reduced the nerve growth factor effect by >90%. Transfer of the cyclic AMP response element to a heterologous (thymidine kinase) promoter activated that promoter approximately 5-fold after nerve growth factor, while transfer of a cyclic AMP response element point-gap mutant (TGA-GTAA) to a heterologous promoter abolished the nerve growth factor effect. These findings indicate that the cyclic AMP response element in cis is, at least in part, both necessary and sufficient to activate the chromogranin A gene. Chemical blockade of the nerve growth factor receptor TrkA or the mitogen-activated protein kinase pathway component MEK substantially diminished nerve growth factor-induced expression of chromogranin A. By contrast, the response of chromogranin A to nerve growth factor was not impaired after blockade of phospholipase C-gamma or phosphoinositide-3 kinase. Chemical blockade of TrkA, Ras, MEK or mitogen-activated protein kinase similarly inhibited nerve growth factor activation of chromogranin A. Expression of constitutively activated Ras, Raf or MEK mutants increased chromogranin A promoter activity. Expression of dominant negative (inhibitory) mutants of Sos, Ha-Ras, Rafl, mitogen-activated protein kinase, ribosomal protein S6 serine kinase II (CREB kinase) or CREB (KCREB) each inhibited the nerve growth factor-induced increase in chromogranin A promoter activity. Thus, each component of the mitogen-activated protein kinase pathway is crucially involved in relaying the nerve growth factor signal in trans to the chromogranin A gene, in the following proposed sequence: nerve growth factor --> TrkA --> Shc/Grb2/Sos --> Ras --> Raf --> MEK --> mitogen-activated protein kinase --> ribosomal protein S6 serine kinase II --> CREB cyclic AMP response element.
...
PMID:Neurotrophin activation of catecholamine storage vesicle protein gene expression: signaling to chromogranin a biosynthesis. 1019 63

Pituitary adenylyl cyclase-activating polypeptide (PACAP) is a potent endogenous secretagogue for chromaffin cells. We previously reported that PACAP coupled to the PAC1 receptor to evoke dihydropyridine-sensitive early (15 to 20 minutes) catecholamine secretion and cAMP response element binding protein-mediated trans-activation of the secretory protein chromogranin A promoter in PC12 pheochromocytoma cells. In this report, we studied whether the secretory and transcriptional responses elicited by PACAP were subject to desensitization. We found that PACAP evoked distinct immediate (initial, 0 to 20 minutes) and long-lasting (20 to 180 minutes) effects on catecholamine secretion. Initial secretory and chromogranin A trans-activation responses induced by PACAP were desensitized in a dose-dependent fashion after preexposure of cells to PACAP, and the IC(50) doses of PACAP for desensitization were approximately 18- to approximately 32-fold lower than the EC(50) activating doses for secretion or transcription. Desensitization of the initial secretion response was associated with decreased Ca(2+) influx through L-type voltage-operated Ca(2+) channels. Acute exposure to PACAP also triggered long-lasting (up to 3 hours), extracellular Ca(2+)-dependent, pertussis toxin-insensitive catecholamine secretion; indeed, even after short-term (20 minutes) exposure to PACAP and removal of the secretagogue, PC12 cells continued to secrete norepinephrine up to 76.9+/-0.22% of cellular norepinephrine content after 3 hours. A phospholipase C-beta inhibitor (U-73122) blocked this extended secretory response, which was dependent on low-magnitude Ca(2+) influx resistant to several L-, N-, P/Q-, or T-type Ca(2+) channel antagonists, but sensitive to Zn(2+), Ni(2+), Cd(2+), or to the store-operated Ca(2+) channel blocker SKF96365. A less than additive effect of the sarco-endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin plus PACAP on this sustained secretion also supported a contribution of store-operated Ca(2+) entry to the sustained secretory response. We propose that PACAP-evoked secretion and transcription are subject to homologous desensitization in PC12 cells; however, PACAP also induces long-lasting secretion, even under dose and time circumstances in which acute, dihydropyridine-sensitive secretion has been desensitized. Although initial secretion is mediated by an L-type voltage-operated Ca(2+) channel, extended secretion may involve a store-operated Ca(2+) channel that is activated through a G(q/11)/phospholipase C-beta/phosphoinositide signaling pathway.
...
PMID:Time-dependent effects of the neuropeptide PACAP on catecholamine secretion : stimulation and desensitization. 1056 98

Nerve growth factor (NGF) initiates the majority of its biological effects by promoting the dimerization and activation of the tyrosine kinase receptor TrkA. In addition to rapid increases in the phosphorylation of phosphatidylinositol 3'-kinase (PI 3-kinase) and phospholipase C-gamma and increased ras activity, phosphorylation of c-Crk and paxillin proteins has been observed upon TrkA activation. The c-Abl tyrosine kinase is involved in the control of the axonal cytoskeleton and is known to interact with c-Crk proteins. Here we have tested the possibility that TrkA receptors might form an association with the c-Abl protein. After transfection in 293T cells, TrkA and c-Abl kinases could be coimmunoprecipitated. This interaction did not require TrkA receptors to be autophosphorylated. Mapping analysis indicated that the region of c-Abl association was confined to the juxtamembrane region of TrkA. The interaction of c-Abl with TrkA was also observed in differentiated pheochromocytoma PC12 cells. These results suggest that c-Abl may be recruited to the NGF receptor complex and be involved in regulating specific phosphorylation events that occur during neuronal differentiation.
...
PMID:Association of the Abl tyrosine kinase with the Trk nerve growth factor receptor. 1067 71

The role of cytokine in neuronal injury was examined in rat pheochromocytoma (PC12) cells under chemical hypoxia (i.e. KCN) and glucose deprivation. The mRNA levels of interleukin-1alpha (IL-1alpha), IL-6, and tumor necrosis factor-alpha (TNF-alpha) were measured by reverse transcription-polymerase chain reaction (RT-PCR) in PC12 cells exposed to 0.5 mM KCN for various time intervals. Cytokine mRNA levels expressed to peak levels 30 minutes after KCN treatment and declined gradually until 240 min. The IL-1alpha activity reached the highest levels 2 hr after the same KCN treatment. Under parallel conditions, KCN increased cytosolic free calcium concentration ([Ca2+]i) in the absence of glucose. However, IL-1alpha mRNA induction by KCN was not altered under calcium-free conditions in PC12 cells, indicating its induction was Ca2+-independent. However, the phosphatidylcholine (PC)-specific phospholipase C (PLC) inhibitor D609 decreased the KCN-induced IL-1alpha mRNA and protein in PC12 cells suggests that PC-PLC might play a role in cytokine induction during hypoxia.
...
PMID:Induction of cytokine genes and IL-1alpha by chemical hypoxia in PC12 cells. 1104 96

The effect of oleamide, a sleep-inducing endogenous lipid in animal models, on intracellular free levels of Ca(2+) ([Ca(2+)](i)) in non-excitable and excitable cells was examined by using fura-2 as a fluorescent dye. [Ca(2+)](i) in pheochromocytoma cells, renal tubular cells, osteoblast-like cells, and bladder cancer cells were increased on stimulation of 50 microM oleamide. The response in human bladder cancer cells (T24) was the greatest and was further explored. Oleamide (10-100 microM) increased [Ca(2+)](i) in a concentration-dependent fashion with an EC(50) of 50 microM. The [Ca(2+)](i) signal comprised an initial rise and a sustained plateau and was reduced by removing extracellular Ca(2+) by 85 +/- 5%. After pre-treatment with 10-100 microM oleamide in Ca(2+)-free medium, addition of 3 mM Ca(2+) increased [Ca(2+)](i) in a manner dependent on the concentration of oleamide. The [Ca(2+)](i) increase induced by 50 microM oleamide was reduced by 100 microM La(3+) by 40%, but was not altered by 10 microM nifedipine, 10 microM verapamil, and 50 microM Ni(2+). In Ca(2+)-free medium, pre-treatment with thapsigargin (1 microM), an endoplasmic reticulum Ca(2+) pump inhibitor, abolished 50 microM oleamide-induced [Ca(2+)](i) increases; conversely, pretreatment with 50 microM oleamide reduced 1 microM thapsigargin-induced [Ca(2+)](i) increases by 50 +/- 3%. Suppression of the activity of phospholipase C with 2 microM U73122 failed to alter 50 microM oleamide-induced Ca(2+) release. Linoleamide (10-100 microM), another sleep-inducing lipid with a structure similar to that of oleamide, also induced an increase in [Ca(2+)](i). Together, it was shown that oleamide induced significant [Ca(2+)](i) increases in cells by a phospholipase C-independent release of Ca(2+) from thapsigargin-sensitive stores and by inducing Ca(2+) entry.
...
PMID:Effect of oleamide on Ca(2+) signaling in human bladder cancer cells. 1170 96

Beta-eudesmol, a sesquiterpenoid isolated from "So-jutsu" (Atractylodis lanceae rhizomas), is known to have various unique effects on the nervous system. We examined in detail the mechanism by which beta-eudesmol modified neuronal function using rat pheochromocytoma cells (PC-12). Beta-eudesmol at concentrations of 100 and 150 microM significantly induced neurite extension in PC-12 cells, which was accompanied, at the highest concentration, by suppression of [(3)H]thymidine incorporation. Beta-eudesmol at concentrations of 100 and 150 microM also evoked a significant increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) in these cells, as determined by the fura 2 assay. Much of this increase remained even after the extracellular Ca(2+) was chelated by EGTA. The [Ca(2+)](i) increase induced by beta-eudesmol was partially inhibited by the phosphoinositide-specific phospholipase C (PI-PLC) inhibitor 1-[6-[[17beta-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U-73122) (2 microM) under extracellular Ca(2+)-free conditions. Furthermore, beta-eudesmol, in a concentration-dependent fashion, caused an accumulation of inositol phosphates. beta-Eudesmol (150 microM) promoted phosphorylation of both mitogen-activated protein kinase (MAPK) and cAMP-responsive element binding protein in a time-dependent manner. These phosphorylations were suppressed by the MAPK kinase inhibitor 2-(2'-amino-3'-methoxyphenol)-oxanaphthalen-4-one (PD98059) (50 microM), U-73122 (2 microM), the calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W7) (1-10 microM), and the protein kinase A inhibitor N-[2-(4-bromocinnamylamino)ethyl]-5-isoquinoline (H89) (1-10 microM). Beta-eudesmol-induced neurite extension was significantly inhibited by both U-73122 (2 microM) and PD98059 (30 microM), suggesting the involvement of PI-PLC and MAPK in neurite outgrowth. Beta-eudesmol, being a small molecule, may therefore be a promising lead compound for potentiating neuronal function. Furthermore, the drug may be useful in helping to clarify the mechanisms underlying neuronal differentiation.
...
PMID:Beta-eudesmol induces neurite outgrowth in rat pheochromocytoma cells accompanied by an activation of mitogen-activated protein kinase. 1202 7

The effects of neomycin, one of the aminoglycoside antibiotics, on the acetylcholine (ACh)-induced current (I(ACh)) were studied in pheochromocytoma cells by using the whole-cell clamp technique. The I(ACh) proved to be generated through neuronal nicotinic receptor. ACh (30 microM) induced an inward current at a holding potential of -80 mV. When cells were treated with neomycin (0.01-1 mM) and ACh (30 microM) simultaneously, an inhibitory effect of neomycin on the peak of I(ACh) was found. This effect was fast, reversible, and concentration dependent. Pretreatment with neomycin for 3-8 min had no effect on the inhibition of I(ACh) induced by neomycin. External application of 0.1 mM neomycin neither shifted the dose-response curve of the peak I(ACh) to the right (dissociation constant (K(d)) = 16.5 microM) nor affected its coefficient (1.8) but inhibited the curve amplitudes by approximately 33%. Stimulated protein kinase C activation by using an exogenous activator produced inhibition of I(ACh), while using protein kinase C inhibitor (PKCI 19-31) had no effect on the inhibition of I(ACh) induced by neomycin. These results suggest that neomycin has an inhibitory effect on I(ACh) without the involvement of phospholipase C. It indicates that neomycin binds to a specific site on the cell membrane, probably on the neuronal nicotinic receptor-coupled channel, and inhibits the I(ACh) in a noncompetitive manner, thus controlling the immediate catecholamine release from the sympathetic cells.
...
PMID:Decrease in acetylcholine-induced current by neomycin in PC12 cells. 1206 99

To assess the role of orexin receptor signaling in neuron-like cells, Neuro-2a murine neuroblastoma and PC12 human pheochromocytoma cells were stably transfected with human OX(1) or OX(2) receptors. Activation of both receptors strongly elevated cellular inositol phosphates and Ca(2+). A difference in the potency between orexin-A and -B was seen for OX(1), but not OX(2) receptors. Dependence of the orexin-mediated Ca(2+) response on extracellular Ca(2+) and the observed Ba(2+) influx indicate that in addition to phospholipase C, orexin receptors also may couple to similar non-voltage-gated Ca(2+) channels in neuronal cells as previously characterized in non-neuronal cells.
...
PMID:Orexin signaling in recombinant neuron-like cells. 1220 95


<< Previous 1 2 3 4 5 Next >>

---