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)

PGJ2 and delta 12PGJ2 (1 microM to 30 microM) inhibited the growth of human astrocytoma cells (1321N1) in a time-dependent manner within 48 hrs, determined by [3H]thymidine incorporation into acid-insoluble fraction or amounts of protein. The EC50 values for PGJ2 and delta 12PGJ2 were approximately 8 microM and 6 microM, respectively. [3H]Thymidine incorporation to acid insoluble fraction was inhibited by these PGs within 1 hr, indicating that these PGs rapidly affect cell functions. Although it has been reported that an increase in cyclic AMP inhibits cell growth, PGJ2 and delta 12PGJ2, but not PGE1, reduced isoproterenol (10 microM)-induced accumulation of cyclic AMP, suggesting that PGJ2 and delta 12PGJ2 may disturb adenylate cyclase system, which might be independent on cell growth. On the other hand, these PGs inhibited the incorporation of [3H]inositol into phospholipid fraction within 6 hrs. Furthermore, PGJ2 and delta 12PGJ2 inhibited carbachol- and/or histamine-induced accumulation of inositol phosphates with a similar dose-dependency to their inhibitions of cell growth. In membrane preparations, however, PGJ2 and delta 12PGJ2 failed to inhibit GTP gamma S (10 microM)- nor Ca2+ (1 mM)-induced accumulation of inositol phosphates. The site of PGJ2 or delta 12PGJ2 in inhibition of inositol phosphate accumulation would not be phospholipase C nor a putative GTP binding protein involved in activation of phospholipase C. The present results indicate that PGJ2 and delta 12PGJ2 inhibit cell growth in human astrocytoma cells and the inhibition of phosphoinositide turnover by these PGs might be involved in the inhibition of cell growth.
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PMID:PGJ2 and delta 12PGJ2 inhibit cell growth accompanied with inhibition of phosphoinositide turnover in human astrocytoma cells. 217 1

By employing early-passaged rabbit kidney epithelial cells in tissue culture, we demonstrated that angiotensin II (AII) has unique mechanisms of signal transduction. First, unlike its action in other target tissues, micromolar concentrations of AII are required to induce small rises in cytosolic calcium, [Ca2+]i, an action which is not accompanied by the release of inositol phosphates (IP). In contrast, nanomolar bradykinin (BK) mobilizes [Ca2+]i through activation of phospholipase C and release of IP. Neither of these stimulated calcium responses exhibits pertussis toxin (PTx) sensitivity. Secondly, AII and BK at 10(-9) to 10(-7) M stimulate cAMP indirectly through PGE2 production in distal cells. AII- and BK-stimulated PGE2 release is PTx inhibitible, suggestive of the presence of a GTP binding protein mediating the response. By contrast, arginine vasopressin fails to elicit rises in [Ca2+]i but exerts its primary effect on cAMP production in distal cells via direct coupling to a stimulatory GTP binding protein, as evidenced by uncoupling with cholera toxin. Regulation of PGE2 synthesis appears to occur via phospholipase A2, not C, by all three peptides.
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PMID:Relationship between phospholipase C activation and prostaglandin E2 and cyclic adenosine monophosphate production in rabbit tubular epithelial cells. Effects of angiotensin, bradykinin, and arginine vasopressin. 244 59

The ability of a variety of agonists to induce formation of inositol phosphates and 1,2-diacylglycerol in cultured adult human keratinocytes has been investigated. Histamine, bradykinin, and thrombin significantly stimulated formation of inositol mono-, bis-, and trisphosphate and 1,2-diacylglycerol within 5 min after addition. Aluminum fluoride also caused a dose-dependent accumulation of inositol phosphates suggesting the participation of a GTP binding protein in the regulation of phospholipase C-catalyzed phosphoinositide hydrolysis. These data demonstrate that human keratinocytes possess the capacity for phospholipase C-mediated signal transduction and suggest that this pathway may participate in the regulation of keratinocyte function.
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PMID:Agonist-induced hydrolysis of phosphoinositides and formation of 1,2-diacylglycerol in adult human keratinocytes. 247 31

Carbachol, histamine and bradykinin activate phospholipase C in pertussis toxin-insensitive manner in human astrocytoma cells. Pretreatments of the cells with these agonists resulted in the reduction of GTP gamma S-induced accumulation of inositol phosphates in membrane preparations. Treatment of cells with carbachol mobilized GTP gamma S binding activities as well as muscarinic receptors from heavy membrane fraction to light fraction, reflecting from an agonist-induced desensitization. The treatment of the cells with agonists reduced a 32 kDa GTP binding protein in heavy membrane fraction, determined by a photoaffinity labeling with [35S]GTP gamma S. The data suggest that the 32 kDa GTP binding protein is involved in desensitization by agonists which activate phospholipase C in human astrocytoma cells.
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PMID:GTP gamma S binding activities were reduced in heavy membrane fraction during desensitization by Ca-mobilizing agonists in human astrocytoma cells. 250 Jun 83

The properties of thromboxane A2 (TXA2) receptors were examined in 1321N1 human astrocytoma cells. 9,11-Epithio-11,12-methanothromboxane A2 (STA2), a stable analogue of TXA2, stimulated the accumulation of inositol phosphates (IPs) with an EC50 of about 50 nM. The STA2-induced accumulation of IPs was inhibited concentration dependently by ONO3708, a TXA2 receptor antagonist, with an inhibition constant (Ki) of about 10 nM. Inositol trisphosphate (IP3) was accumulated more rapidly than inositol bisphosphate (IP2) in response to STA2. HPLC analysis indicated that inositol 1,4,5-trisphosphate accumulated in the presence of STA2. STA2 alone had no effect on the accumulation of IPs in membrane preparations but it potentiated the accumulation induced by GTP gamma S. [3H]SQ29548, a TXA2 receptor antagonist, bound specifically to TXA2 receptors, expressing a single binding site with a dissociation constant (Kd) of 10.9 nM. The competition curve for STA2 inhibition of [3H]SQ29548 binding was shifted to the right and was steeper in the presence of GTP gamma S. Pertussis toxin (IAP) elicited ADP-ribosylation of 41KD protein but had no effect on the sensitivity to GTP of the STA2 inhibition of SQ29548 binding or of STA2-induced accumulation of IPs. It is concluded from these results that the stimulation of TXA2 receptors results in activation of phospholipase C via a GTP binding protein and that the protein is not a substrate for IAP.
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PMID:Thromboxane A2 activates phospholipase C in astrocytoma cells via pertussis toxin-insensitive G-protein. 254 56

The m1 muscarinic acetylcholine receptor gene was transfected into and stably expressed in A9 L cells. The muscarinic receptor agonist, carbachol, stimulated inositol phosphate generation, arachidonic acid release, and cAMP accumulation in these cells. Carbachol stimulated arachidonic acid and inositol phosphate release with similar potencies, while cAMP generation required a higher concentration. Studies were performed to determine if the carbachol-stimulated cAMP accumulation was due to direct coupling of the m1 muscarinic receptor to adenylate cyclase via a GTP binding protein or mediated by other second messengers. Carbachol failed to stimulate adenylate cyclase activity in A9 L cell membranes, whereas prostaglandin E2 did, suggesting indirect stimulation. The phorbol ester, phorbol 12-myristate 13-acetate (PMA), stimulated arachidonic acid release yet inhibited cAMP accumulation in response to carbachol. PMA also inhibited inositol phosphate release in response to carbachol, suggesting that activation of phospholipase C might be involved in cAMP accumulation. PMA did not inhibit prostaglandin E2-, cholera toxin-, or forskolin-stimulated cAMP accumulation. The phospholipase A2 inhibitor eicosatetraenoic acid and the cyclooxygenase inhibitors indomethacin and naproxen had no effect on carbachol-stimulated cAMP accumulation. Carbachol-stimulated cAMP accumulation was inhibited with TMB-8, an inhibitor of intracellular calcium release, and W7, a calmodulin antagonist. These observations suggest that carbachol-stimulated cAMP accumulation does not occur through direct m1 muscarinic receptor coupling or through the release of arachidonic acid and its metabolites, but is mediated through the activation of phospholipase C. The generation of cytosolic calcium via inositol 1,4,5-trisphosphate and subsequent activation of calmodulin by m1 muscarinic receptor stimulation of phospholipase C appears to generate the accumulation of cAMP.
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PMID:A transfected m1 muscarinic acetylcholine receptor stimulates adenylate cyclase via phosphatidylinositol hydrolysis. 255 56

Ca-dependent K and Cl currents were measured in isolated cells from rat lacrimal glands using the tight-seal whole-cell recording method. Upon application of acetylcholine (ACh), both K and Cl-selective currents were activated. The size of the ACh-activated currents declined after a few minutes of whole-cell recording. The rundown curve was composed of an initial stable period followed by a rather rapid decline. Both the length of the initial plateau and the speed of the falling phase were dependent on cell size and recording pipette resistance. The results suggest that the rundown was due to washout of an unknown cytosolic substance. Another manifestation of washout was an increase in the delay of the response. Plots of the inverse of the delay as a function of time in whole-cell recording showed again an initial plateau and a falling phase, but the stable period lasted less than in amplitude plots. Analysis of the washout time course suggested that the cytosolic substance has a diffusion coefficient of 5.4 x 10(-6) cm2/s, corresponding to a molecular weight of 350. Washed-out cells were insensitive to GTP-gamma-S, but responded normally to an internal application of inositol-trisphosphate (InsP3), introduced through the pipette. Thus, the step of the response which is sensitive to washout is closely related to the production of InsP3. Addition of various exogenous water soluble substances failed to halt washout. Among the inactive substances were GTP (or a combination of Mg and GTP) and small water soluble precursors of InsP3. The results imply that the production of InsP3 by muscarinic agonists in exocrine glands requires the presence of a small molecular weight, water soluble substance. It is suggested that this substance is an unknown co-factor of phospholipase C or of Gp, the GTP binding protein governing the production of InsP3.
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PMID:Diffusion into the patch-clamp recording pipette of a factor necessary for muscarinic current response. 270 3

The O2- production as a marker of the respiratory burst was investigated under various stimulations in polymorphonuclear leukocytes of healthy young and aged subjects. Stimulation of the respiratory burst in the cells of elderly by specific agents (opsonized zymozan, N-formyl-methionyl-leucyl-phenylalanine, carbachol) resulted in a diminished response while it remained unchanged on the effect of non-specific stimulation (A23187, phorbol myristate acetate) comparing to young subjects. To elucidate the postreceptor signal transduction mechanism involved in respiratory burst stimulation various inhibitors were used as follows: neomycin (for phospholipase C enzyme), mepacrine (for phospholipase A2 enzyme) and pertussis toxin (for GTP binding regulatory protein). The results suggest that phospholipase C as well as phospholipase A2 could be involved in the postreceptor signal transduction depending on the stimulus, but the impairment of the pertussis toxin sensitive GTP binding protein with aging might explain the decrease response of the respiratory burst after stimulating the different receptors.
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PMID:Studies on opsonized zymozan, FMLP, carbachol, PMA and A23187 stimulated respiratory burst of human PMNLs. 284 40

1. Activation of vascular smooth muscle by angiotensin II results in the generation of two second messengers, inositol trisphosphate (IP3) and diacylglycerol (DG). 2. IP3 is responsible for mobilizing calcium from endoplasmic reticulum. This signal is transient, most likely serving to initiate calcium events leading to contraction, and is attenuated by activation of protein kinase C. 3. DG stimulates protein kinase C and ultimately Na+/H+ exchange, leading to intracellular alkalinization. Accumulation of DG/activation of protein kinase C is sustained, and may be enhanced by concurrent intracellular alkalinization. The delay in induction of the sustained response appears to be related to cellular processing of the angiotensin II-receptor complex. 4. Angiotensin II-stimulated, phospholipase C-mediated IP3 formation is also modulated by a pertussis toxin-insensitive guanine nucleotide regulatory protein. 5. The GTP binding protein, movement of the receptor-ligand complex, and the signals generated by the two second messengers, IP3 and DG, interact in a complex manner to cause an integrated response of vascular smooth muscle cells to angiotensin II stimulation.
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PMID:Secondary signalling mechanisms in angiotensin II-stimulated vascular smooth muscle cells. 307 71

Interleukin-2 (IL-2) is a polypeptide growth factor which stimulates the proliferation and differentiation of T lymphocytes. The receptor for IL-2 is expressed on activated T lymphocytes, cloned IL-2 dependent cells and several other cell types. Analysis of the primary structure and of immune-precipitated receptor suggests that this molecule has no intrinsic signal transduction function, unlike other growth factors. IL-2 interaction with a high affinity receptor has been shown, however, to activate the calcium/phospholipid-dependent protein kinase C (PK-C) presumably via phosphoinositide hydrolysis. Members of a family of closely related guanine nucleotide binding proteins (G proteins) regulate a diverse group of metabolic events. Two of them, Gs and Gi, stimulate and inhibit adenylate cyclase activity respectively, and other G proteins are involved in diverse signal transduction system. Another member, Go, has no known function and activation of phospholipase C has been attributed to the action of an unidentified G protein, Gp. Since it has been observed that IL-2 inhibits the catalytic activity of adenylate cyclase and that agents such as PGE2 which stimulate adenylate cyclase activity inhibit the lymphoproliferative response to IL-2, association of GTP binding proteins with IL-2 signal transduction was investigated. In this report we describe for the first time the participation of a GTP binding protein in the action of a polypeptide growth factor, interleukin-2.
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PMID:Stimulation of specific GTP binding and hydrolysis activities in lymphocyte membrane by interleukin-2. 310 Sep 64


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