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)

Although it is well known that endothelial cells transport serotonin (5-HT) from extracellular to intracellular locations, it has been generally assumed that smooth muscle cells do not accumulate 5-HT but, rather, respond to 5-HT through a receptor activity unrelated to uptake of this amine or via stimulation of endothelial-derived relaxing factor. In the present study smooth muscle cells (PASMC), isolated and cultured from bovine pulmonary artery, were evaluated for 5-HT uptake under a variety of conditions. 5-HT uptake was linear up to 15 min and the rate was seven- to eightfold higher than that by bovine pulmonary artery endothelial cells. There was intracellular metabolism of 5-HT to 5-hydroxyindoleacetic acid (5-HIAA). The uptake was inhibited by exposure to 4 degrees C, absence of Na+ from the medium, and agents such as imipramine, verapamil, ketanserin, and methiothepin. Like that of endothelial cells, 5-HT uptake by PASMC was stimulated by exposure of cells to anoxia for 24 hr. Unlike endothelial cells that showed no morphological changes, PASMC at early passage showed dendritic formation after 30-60 min exposure to 5-HT at a concentration as low as 10(-8) M. Although this configurational change in response to 5-HT was lost with passage of cells, transport of 5-HT by these cells was retained. The configurational change was blocked by agents that inhibited 5-HT uptake, such as imipramine, verapamil, ketanserin, and methiothepin; it was unaffected by inhibitors of protein kinase C, phospholipase C, and calmodulin or absence of Ca2+ from the medium. We conclude that PASMC, as well as endothelial cells, accumulate 5-HT; there appears to be a close relationship between 5-HT uptake and configurational change of early passaged PASMC in culture. The factor(s) required for the configurational change are absent in endothelial cells and lost during passage of PASMC.
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PMID:Serotonin uptake and configurational change of bovine pulmonary artery smooth muscle cells in culture. 264 13

1. In a crustacean neuromuscular preparation, the walking leg opener muscle of the freshwater crayfish Procambarus clarkii, application of serotonin (1 microM) produces presynaptic depolarization and long-lasting facilitation of excitatory postsynaptic potentials (EPSPs). The frequency of spontaneously released transmitter quanta also increases. Facilitation of evoked EPSPs declines after serotonin application in two phases. 2. Serotonin-induced facilitation was examined using simultaneous pre- and postsynaptic intracellular microelectrode recording. A presynaptic microelectrode recorded action potentials and membrane potential of a presynaptic axonal branch, and one or more postsynaptic microelectrodes recorded EPSPs in muscle fibers innervated by the excitatory motor axon. Components of the phosphatidylinositol second messenger system and pharmacologic agents affecting this system were injected through the presynaptic electrode, and changes in synaptic transmission were measured. 3. Presynaptic injection of inositol 1,4,5-triphosphate (IP3) causes presynaptic depolarization, increases the frequency of spontaneously released transmitter quanta, and promotes a relatively short-lasting facilitation of evoked EPSPs. These actions are consistent with elevation of intracellular Ca2+ and resemble the early phase of serotonin-induced facilitation. 4. Application of a phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), that activates protein kinase C (C-kinase), produces a long-lasting, low-level facilitation of evoked EPSPs. Application of another phorbol ester, phorbol-12-monoacetate (PTMA), which does not activate C-kinase has no effect. 5. Presynaptic injection of RA 233, a phospholipase C (PLP-C) inhibitor, blocks all aspects of serotonin-induced facilitation. This compound was found to have no general deleterious effects on synaptic transmission and does not block other forms of synaptic facilitation in this preparation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phosphatidylinositol system's role in serotonin-induced facilitation at the crayfish neuromuscular junction. 275 75

Serotonin-stimulated activation of phospholipase C in primary astroglial cell cultures was studied as a mean of evaluating the effect of acute ethanol exposition on this signal transduction system. The addition of 50-150 mM ethanol prior to stimulation with 10(-5) M serotonin led to a potentiation of the serotonin-induced [3H]-inositol phosphate formation and an increased incorporation of [3H]-inositol into the three phosphoinositides studied. This potentiating effect of ethanol was observed only when ethanol was added together with serotonin. No stimulatory effect of ethanol per se was found. Furthermore, ethanol had no effect on arginine-vasopressin, bradykinin or phenylephrine stimulated inositol lipid metabolism.
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PMID:Ethanol potentiates serotonin stimulated inositol lipid metabolism in primary astroglial cell cultures. 277 5

Calf serum induced the phospholipase C-mediated hydrolysis of phosphoinositides in normal rat kidney (NRK) cells transformed by a temperature-sensitive Kirsten murine sarcoma virus (tsK-NRK cells). Various growth factors known to induce the phospholipase C reactions in other cell types, such as platelet-derived growth factor, fibroblast growth factor, epidermal growth factor, thrombin, vasopressin, bombesin, cholecystokinin, and prostaglandin F2 alpha, did not induce phospholipase C reactions in the transformed NRK cells. Furthermore, noradrenaline, histamine, dopamine, angiotensin II, carbachol, and tumor growth factor-beta did not induce phospholipase C reactions. However, serotonin did induce phospholipase C reactions. The amount of serotonin contained in the calf serum was sufficient to support 50% of the activity promoted by the serum itself, and calf serum-induced phospholipase C reactions were inhibited to 10-20% of the original level by ketanserin and methysergide, known to be antagonists for the serotonin receptors. Dialysis almost completely removed serotonin from calf serum and reduced the serum-induced phospholipase C reactions. Moreover, the phospholipase C reactions induced by calf serum and serotonin were inhibited by pretreatment of the cells with pertussis toxin or 12-O-tetradecanoylphorbol-13-acetate. These results indicate that serotonin is one of the major serum factors inducing phospholipase C-mediated hydrolysis of phosphoinositides in transformed NRK cells. Serotonin induced phospholipase C reactions not only in tsK-NRK cells but also in nontransformed NRK cells. However, serotonin did not induce these reactions in Swiss 3T3 cells or NIH 3T3 cells.
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PMID:Serotonin as a major serum factor inducing the phospholipase C-mediated hydrolysis of phosphoinositides in normal rat kidney cells. 284 56

Serotonin (5-HT), histamine (HA), angiotensin II (ATII), prostaglandin F2 alpha (PGF2 alpha) and thromboxane A2 (TxA2) are known as vasoactive substances, each producing a characteristic contraction of cerebral arteries. These contractions are considered to be mediated by their specific receptors. Recent studies suggest that the activations of these receptors primarily stimulate the phospholipase C and/or phospholipase A2 localized within the same membrane. Stimulation of these enzymes consequently induces production of the second or third messengers such as inositol triphosphate (IP3), diacylglyceride (DAG), arachidonic acid (AA), and ultimately various prostaglandins. The present study is to examine how oxyhemoglobin (Oxy-Hb), another vasoactive substance, can modify these receptor-mediated contractions, and to compare the effects on high K+-, caffeine-and 1-oleoyl-2-acetyl-rac-glycerol (OAG)-induced contractions which are not mediated by the receptors on the cytoplasmic membrane. Helical strips of the bovine middle cerebral arteries (M2) were mainly used in this experiment, and the changes in muscular tensions during isometric contractions were recorded on the polygraph. 5-HT, HA, ATII, PGF2 alpha and cTxA2 (carbocyclic thromboxane A2) were used for each receptor activation. Indomethacin (IDM), a cyclooxygenase inhibitor and 2-nitro-4-carboxyphenyl-n, n-diphenyl-carbamate (NCDC), a phospholipase C inhibitor were used to analyze a possible acting site of Oxy-Hb in modifying these reseptor-mediated enzyme reactions. The results obtained are summarized as follows. (1) All contractions induced by either 5-HT, PGF2 alpha, cTxA2, HA or ATII (concentrations less than 10(-6) M) were markedly augmented as much as 4-8 times the normal, when they were examined in the presence of 10(-5)M Oxy-Hb.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Selective augmenting effect of oxy-Hb on the contractions of cerebral arteries elicited by various vasoactive substances]. 290 26

The mechanisms of growth factor action were studied in a fibroblastic cell line capable of reversible growth arrest in G0-G1. This cell line, derived from Chinese hamster lung, can be stimulated to divide by a limited set of purified growth factors, including EGF, FGF, PDGF, alpha-thrombin (THR), serotonin (5-HT) and insulin. THR and 5-HT stimulate, via a G-protein (Gp), a polyphosphoinositide-specific phospholipase C (PtdIns(4,5)P2-PLC). In contrast, the mitogens EGF, FGF, PDGF, and insulin do not stimulate PtdIns(4,5)P2-PLC unless this pathway has been preactivated by THR or AlF-4. Finally, from the specific inhibitory action of pertussis toxin on THR- and 5-HT-induced DNA synthesis, and from the exploitation of the 5-HT pharmacological tools, we conclude that: (i) there are at least two distinct G-proteins involved in signalling growth: Gp, coupling receptors to PtdIns(4,5)P2-PLC, and Gi, coupling receptors negatively to adenylyl cyclase and probably to other unknown effector(s); (ii) activation of receptor-tyrosine kinases provides an alternate growth factor signalling pathway, independent of Gp- and Gi-mediated actions; and (iii) tyrosine kinases positively 'cross-communicate' with the inositol-lipid pathway (phosphorylation of Gp, PLC, PtdIns kinases...?).
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PMID:Transmembrane signalling pathways initiating cell growth in fibroblasts. 290 48

In order to explore the cellular mechanisms responsible for the vascular abnormalities observed in hypertension, smooth muscle cells (SMC) were cultured after enzymatic digestion of aortas from both normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). These cultures were performed in the presence of fetal calf serum (FCS) and stimulated by vasoactive agents (angiotension II, serotonin, bradykinin). Growth rate was determined by cell counting and measurement of nuclear-tritiated thymidine incorporation and phospholipase C (PLC) activation by measurement of 3h-inositol mono-, di-, tri-, and tetra-phosphates formed from preincorporated 3h-myo-inositol. Cells from SHR proliferate more actively than control ones in the presence of 10% FCS but don't significantly differ at lower concentrations. In the presence of 5% FCS angiotensin II (10(-7) mol/L), 5-HT (10(-6) mol/L) and bradykinin (10(-6) mol/L) enhance cell proliferation and their effect is more important in cultures from SHR. The phospholipase C activation induced by these drugs was also more important in these SHR cultures than in control ones. The PLC hyperreactivity observed in SHR cells may therefore be involved in their enhanced proliferating activity evidenced in culture and in the vascular abnormalities described in vivo.
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PMID:Enhanced proliferating activity of cultured smooth muscle cells from SHR. 291 46

Platelet-activating factor (PAF), which is thought to cause platelet aggregation and degranulation via a receptor-mediated activation of phospholipase C, had no direct action on PGE1-stimulated cyclic AMP formation in intact human platelets, although it caused a GTP and Na+-dependent inhibition of the adenylate cyclase activity of human platelet particulate fractions. Studies with PAF analogues indicated that the receptors mediating this inhibition of adenylate cyclase had structural specificity very similar or identical to that of the receptors mediating platelet aggregation. These results suggest that the PAF receptors linked to the activation of phospholipase C in intact platelets may, in membrane preparations, become coupled to the inhibition of adenylate cyclase via the guanine nucleotide-binding protein, Gi. Studies with permeabilized human platelets that secrete 5-HT on addition of low concentrations of Ca2+ showed that addition of either PAF or a guanine nucleotide decreased the Ca2+ required for secretion. When added together, PAF and GTP promoted secretion synergistically at low Ca2+ concentrations. Enhanced secretion of 5-HT was associated with increased formation of diacylglycerol. These results show that PAF can stimulate phospholipase C by both GTP-dependent and independent mechanisms. In intact human platelets, PAF receptors may interact preferentially with a guanine nucleotide-binding protein that promotes phosphoinositide breakdown by phospholipase C, rather than with Gi.
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PMID:Receptor-effector coupling in platelets: roles of guanine nucleotides. 301 Jun 68

Serotonin (5-HT) plays important roles in various behavioral and physiological processes in Aplysia californica. These include feeding, locomotion, circadian rhythm, learning and memory, synaptic plasticity, and synaptic growth. Serotonin modulates these various functions by interacting with different 5-HT receptor subtypes that are coupled to various second-messenger systems. We report here the isolation and characterization of the first two serotonergic receptors from Aplysia californica, Ap5-HTB1 and Ap5-HTB2, using a strategy based on the amino acid sequence homology among G-protein-coupled biogenic amine receptors. Ap5-HTB1 and Ap5-HTB2 are both intronless and highly homologous to each other, sharing 79.5% sequence identity at the amino acid level. Sequence comparison reveals that these receptors are 33.1 to 23.3% identical to the following 5-HT receptors: 5-HTdro1 > 5-HT6 > 5-HTlym > mouse 5-HT1B > 5-HTdro2A > mouse 5-HT7 > rat 5-HT2A. Both Ap5-HTB1 and Ap5-HTB2 encode functional 5-HT receptors. When expressed in cultured cells, these receptors stimulate phospholipase C in response to 5-HT in a dose-dependent manner. This stimulation can be blocked by specific 5-HT receptor antagonists. Using RT-PCR and Western blot analysis, we have detected these receptors in the CNS (Ap5-HTB2) and in the reproductive system (Ap5-HTB1). The nucleotide sequences of Ap5-HTB1 and Ap5-HTB2 were submitted to GenBank; the accession numbers are L43557 and L43558, respectively.
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PMID:Cloning and characterization of two related serotonergic receptors from the brain and the reproductive system of Aplysia that activate phospholipase C. 747 9

The effects of U-73122, a phospholipase C (PLC) inhibitor, on pressor responses to angiotensin II (ANG II), norepinephrine (NE), serotonin (5-HT), BAY K 8644, and the thromboxane A2 (TxA2) mimic, U-46619, were studied in the pulmonary vascular bed of the intact-chest cat. Under conditions of constant lobar blood flow, injections of ANG II, NE, 5-HT, U-46619, and the calcium channel opener, BAY K 8644, into the lobar arterial perfusion circuit caused dose-related increases in lobar arterial pressure, which were reproducible with respect to time. Infusion of U-73122, a PLC inhibitor, into the perfused lobar artery at 10-100 micrograms/kg for 10 min significantly reduced responses to ANG II, serotonin, and NE; however, U-73122 did not alter responses to BAY K 8644 or to U-46619. In a separate series of animals, the effects of the myosin light chain kinase inhibitor, KT-5926, were investigated, and after infusion of KT-5926 into the perfused lobar artery at 1-2 micrograms/kg for 10 min, responses to ANG II, NE, 5-HT, BAY K 8644, and U-46619 were reduced significantly. In a final series of experiments, the effects of the L-type calcium channel blocker, nicardipine, were investigated, and infusion of the L-type calcium channel blocker into the perfused lobar artery at 0.5-1 microgram/kg for 10 min reduced responses to ANG II, BAY K 8644, and NE. However, nicardipine did not alter pressor responses to 5-HT or the TxA2 mimic, U-46619.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of PLC and MLCK inhibitors and the role of L-calcium channels in the cat pulmonary vascular bed. 748 23


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