Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incubation of rat peritoneal mast cells with substance P resulted in the transient stimulation of phosphoinositol breakdown and histamine secretion through an exocytotic process. These effects were inhibited markedly by a prior 2-hr exposure of the cells to pertussis toxin. Pertussis toxin also inhibited exocytosis induced by substance P, mastoparan and compound 48/80, but did not modify the secretory effect of the ionophore A23187. The transfer of rat peritoneal mast cells from balanced salt solution to calcium-free buffer led to a similar time-dependent decrease in their response to substance P and mastoparan. The concomitant absence of potassium from the calcium-free buffer enabled the mast cells to retain their secretory response. These data demonstrate identical dependency for calcium and monovalent ions of the secretory process elicited by substance P, mastoparan and compound 48/80. Pretreatment of mast cells with neuraminidase decreased the secretagogic effect of substance P, mastoparan and compound 48/80 without modifying the efficiency of the ionophore A23187. Thus, sialic acid residues might be involved in the initial binding of peptides and compound 48/80 to mast cells, which activate a pertussis toxin-sensitive G-protein and allows the increase in phospholipase C activity to induce exocytosis. This sequence of events might characterize the physiological pathway of mast cell activation by peptides, without necessarily requiring selective membrane receptors.
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PMID:Activation of rat peritoneal mast cells by substance P and mastoparan. 247 89

Brain tissue and serum from mice intracerebrally injected with 1 microgram of staphylococcal alpha-toxin contained elevated amounts of a naturally occurring brain tissue component(s) called muscle-relaxing factor (MRF). MRF induced reversible, generalized, flaccid paralysis of mice after intracerebral but not intraperitoneal or intravenous administration. MRF (i) was soluble in Hanks balanced salt solution and in acidified (pH 2) Hanks balanced salt solution, in which it partitions into ethyl acetate, acetone, and methanol; (ii) was separated from some pigments by thin-layer chromatography on silica gel plates; (iii) did not comigrate with prostaglandin and leukotriene standards during high-pressure liquid chromatography with a mu Bondapak fatty acid column; and (iv) did not contain amino acids, exhibit absorption maxima at a wavelength range of 210 to 600 nm, or fluoresce when exposed to UV light. MRF has been detected in rabbit brain that has been stored frozen at -70 degrees C and has been enhanced in vitro in slices of both mouse and rabbit brain following incubation of the brain slices with staphylococcal alpha-toxin. Studies to identify the chemical nature of MRF and the mechanism by which, in mice, it induces reversible, flaccid paralysis of voluntary muscle are continuing.
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PMID:Induction of muscle-relaxing factor by staphylococcal alpha-toxin. 830 Feb 2

Schwann cells play an important role in both the development and regeneration of peripheral nerves. Proliferation and differentiation of Schwann cells are critically dependent on changes in the levels of cAMP. ATP is a fast excitatory transmitter in the peripheral nervous system, inducing depolarization of the vagus nerve through occupancy of P2-purinergic receptors. In the present study we demonstrate that extracellular ATP stimulates phospholipase C and inhibits adenylate cyclase activities in cultured Schwann cells. Addition of ATP inhibited, in a concentration-dependent manner, forskolin- or isoprenaline-stimulated adenylate cyclase activity. The rank order of potency corresponding to different purinergic receptor agonists was 2-methylthio-ATP > ATP = ADP > or = adenosine 5'-[gamma-thio]triphosphate (ATP[S]) > UTP, consistent with the involvement of a P2y subtype. Adenosine and adenosine 5'-[alpha,beta-methylene]-triphosphate (pp[CH2pA) were ineffective. Preincubation with pertussis toxin completely blocked this inhibitory effect. When Schwann cells were pre-labelled with myo-[3H]inositol and incubated in Hanks' balanced salt solution containing Ca2+ and Mg2+, addition of ATP[S] resulted in a concentration-dependent increase in the release of InsP with a concomitant increase in intracellular free [Ca2+] ([Ca2+]i). Under these conditions, the effects of both ATP and UTP were of lower magnitude. Removal of Ca2+ and Mg2+ from the assay medium resulted in a significant increase in the effects of ATP[S], ATP and UTP. The decreased response observed in the presence of both bivalent cations (1.2 mM Ca2+ and 1 mM Mg2+) could not be explained either by increased degradation of ATP by Ca2+/Mg2+-dependent nucleotidases or by cation influx. The rank order of potency for the effects of agonists on phospholipase C activity was ATP[S] = adenosine 5'[gamma-imido]triphosphate > ATP -UTP > ADP, indicating the involvement of a P(2U) receptor subtype in this response. Adenosine, AMP and pp[CH2]pA were ineffective. These results demonstrate that immortalized Schwann cells express P(2U) and P(2Y) purinoceptors, which are coupled to stimulation of phospholipase C and inhibition of adenylate cyclase, respectively. Our observations unveil signal-transduction pathways that may be used by ATP to regulate proliferation and differentiation of Schwann cells, and ultimately to influence nerve homeostasis.
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PMID:P2-purigenic receptors regulate phospholipase C and adenylate cyclase activities in immortalized Schwann cells. 867 70

Ca(2+) signaling plays an important role in endothelial cell (EC) responses to shear stress generated by blood flow. Our previous studies demonstrated that bovine fetal aortic ECs showed a shear stress-dependent Ca(2+) influx when exposed to flow in the presence of extracellular ATP. However, the molecular mechanisms of this process, including the ion channels responsible for the Ca(2+) response, have not been clarified. Here, we demonstrate that P2X4 purinoceptors, a subtype of ATP-operated cation channels, are involved in the shear stress-mediated Ca(2+) influx. Human umbilical vein ECs loaded with the Ca(2+) indicator Indo-1/AM were exposed to laminar flow of Hanks' balanced salt solution at various concentrations of ATP, and changes in [Ca(2+)](i) were monitored with confocal laser scanning microscopy. A stepwise increase in shear stress elicited a corresponding stepwise increase in [Ca(2+)](i) at 250 nmol/L ATP. The shear stress-dependent increase in [Ca(2+)](i) was not affected by phospholipase C inhibitor (U-73122) but disappeared after the chelation of extracellular Ca(2+) with EGTA, indicating that the Ca(2+) increase was due to Ca(2+) influx. Antisense oligonucleotides designed to knockout P2X4 expression abolished the shear stress-dependent Ca(2+) influx seen at 250 nmol/L ATP in human umbilical vein ECs. Human embryonic kidney 293 cells showed no Ca(2+) response to flow at 2 micromol/L ATP, but when transfected with P2X4 cDNA, they began to express P2X4 purinoceptors and to show shear stress-dependent Ca(2+) influx. P2X4 purinoceptors may have a "shear-transducer" property through which shear stress is perceived directly or indirectly and transmitted into the cell interior via Ca(2+) signaling.
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PMID:Fluid shear stress activates Ca(2+) influx into human endothelial cells via P2X4 purinoceptors. 1096 36