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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of the cAMP messenger system was found to cause specific changes in angiotensin-II (All)-induced inositol phosphate production and metabolism in bovine adrenal glomerulosa cells. Pretreatment of [3H]inositol-labeled glomerulosa cells with 8-bromo-cAMP (8Br-cAMP) caused both short and long term changes in the inositol phosphate response to stimulation by All. Exposure to 8Br-cAMP initially caused dose-dependent enhancement (ED50 = 0.7 microM) of the stimulatory action of All (50 nM; 10 min) on the formation of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and its immediate metabolites. This effect of 8Br-cAMP was also observed in permeabilized [3H]inositol-labeled glomerulosa cells in which degradation of Ins(1,4,5)P3 was inhibited, consistent with increased activity of phospholipase-C. Continued exposure to 8Br-cAMP for 5-16 h caused selective enhancement of the All-induced increases in D-myo-inositol 1,3,4,6-tetrakisphosphate [Ins(1,3,4,6)P4] and myo-inositol 1,4,5,6-tetrakisphosphate. The long term effect of 8Br-cAMP on the 6-phosphorylated InsP4 isomers, but not the initial enhancement of Ins(1,4,5)P3 formation, was inhibited by cycloheximide. The characteristic biphasic kinetics of All-induced Ins(1,4,5)P3 formation were also changed by prolonged treatment with 8Br-cAMP to a monophasic response in which Ins(1,4,5)P3 increased rapidly and remained elevated during All stimulation. In permeabilized glomerulosa cells treated with 8Br-cAMP for 16 h, the conversion of D-myo-inositol 1,3,4-trisphosphate [Ins(1,3,4)P3] to Ins(1,3,4,6)P4 was consistently increased, whereas dephosphorylation of Ins(1,4,5)P3 to D-myo-inositol 1,4-bisphosphate and of D-myo-inositol 1,3,4,5-tetrakisphosphate to Ins(1,3,4)P3, was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1990 Nov
PMID:Modulation of agonist-induced inositol phosphate metabolism by cyclic adenosine 3',5'-monophosphate in adrenal glomerulosa cells. 228 Jul 73

beta-Bungarotoxin (beta-BTX) isolated from the venom of Bungarus multicinctus has previously been reported to be a neurotoxic protein. The toxin is composed of two subunit chains, denoted A and B. The intact toxin was first examined in this study for its ability to block central nerve ending K channels using the 86Rb efflux technique. beta-BTX, when preincubated with synaptosomes for 30 min in the absence of extracellular Ca2+, selectively inhibited the slowly inactivating voltage-dependent (S) component of 86Rb efflux. The EC50 for inhibition is 1 to 3 nM. The two subunit chains were separated and isolated by reduction and carboxymethylation of the parent toxin. The K channel-blocking activity was associated only with the reduced and carboxymethylated B-subunit of beta-BTX (RCM-B). The dose-dependent inhibition by RCM-B exhibited an apparent biphasic response, with the noninactivating voltage-gated K channel being more susceptible to RCM-B inhibition (EC50 = 0.1 to 0.3 nM) than to inhibition by the parent compound. Additionally, the inactivating voltage-gated K channel (T) was sensitive to inhibition by higher concentrations of RCM-B (EC50 = 1 to 3 nM). These results suggest that the B-chain of beta-BTX may be responsible for blockade of certain voltage-gated K channels in a manner that is not directly related to the known phospholipase activity of the intact molecule.
Mol Pharmacol 1990 Aug
PMID:Potassium channel blockade by the B subunit of beta-bungarotoxin. 238 29

This study was designed to clarify the biochemical mechanism of reperfusion arrhythmias. Forty-three anesthetized dogs were divided into three groups; the occlusion group (n = 7), the reperfusion group (n = 24), and a group treated with the alpha 1-adrenergic blocker, bunazosin (n = 12). In the occlusion group, the left anterior descending coronary artery (LAD) was occluded for 15 min. In the reperfusion group and the bunazosin group, LAD was occluded for 15 min and then reperfused for 5 min with physiological saline or bunazosin (0.5 mg/kg) infused 5 min prior to the LAD occlusion. Seven dogs (29%) of the reperfusion group developed reperfusion arrhythmias, but 17 did not. In the bunazosin group, none developed arrhythmias. Immediately after the end of occlusion or reperfusion, myocardial plasma membrane and mitochondria were prepared from the normal and ischemic areas or the normal and reperfused areas. Phospholipase activity, phospholipid content, and free fatty acid (FFA) levels were determined. The mitochondrial calcium content was also measured. In the reperfusion-with-arrhythmias group, the content of calcium in the mitochondria obtained from the reperfused area and phospholipase activity in the reperfused myocardium was elevated significantly compared with those in the reperfusion-without-arrhythmias group. Phospholipid content in the plasma membrane prepared from the reperfused area also decreased significantly in the reperfusion-with-arrhythmias group. The FFA levels in the plasma membrane prepared from the reperfused area were increased. In the reperfusion-without-arrhythmias group and the bunazosin group, these changes were not observed. Fifteen minutes occlusion alone did not induce these changes observed in the reperfusion-with-arrhythmias group.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1987 Oct
PMID:Biochemical basis for reperfusion arrhythmias. 244 92

1. Depolarization of excitable cells of the central nervous system results in the formation of the second messengers cyclic AMP, cyclic GMP, inositol phosphates, and diacylglycerides. 2. Depolarization-evoked accumulation of cyclic AMP in brain preparations can be accounted for mainly by the release of adenosine, which subsequently interacts with stimulatory adenosine receptor linked to adenylate cyclase. 3. Depolarization-evoked formation of cyclic GMP in brain preparations is linked to activation of voltage-dependent calcium channels, presumably leading to activation of guanylate cyclase by calcium ions. 4. In brain slices depolarization-evoked stimulation of phosphoinositide breakdown and subsequent formation of inositol phosphates and diacylglycerides are linked to activation of voltage-dependent calcium channels, which are sensitive to dihydropyridines, presumably leading to activation of phospholipase(s) C by calcium ions. 5. In the synaptoneurosome preparation depolarization-evoked stimulation of phosphoinositide breakdown does not involve activation of dihydropyridine-sensitive calcium channels and, instead, appears to be regulated primarily by the intracellular concentration of sodium ions. Thus, agents that induce increases in intracellular sodium--such as toxins that open or delay inactivation of voltage-dependent sodium channels; ouabain, an inhibitor of Na+/K+ ATPase that transports sodium outward and a sodium ionophore--all stimulate phosphoinositide breakdown. Mechanistically, increases in intracellular sodium either might directly affect phospholipase(s) C or might lead to influx of calcium ions through Na+/Ca2+ transporters. 6. Depolarization-evoked stimulation of cyclic AMP formation and phosphoinositide breakdown can exhibit potentiative interactions with responses to receptor agonists, thereby providing mechanisms for modulation of receptor responses by neuronal activity. 7. Since all these second messengers can induce phosphorylation of ion channels through the activation of specific kinases, it is proposed that depolarization-evoked formation of second messengers represents a putative feedback mechanism to regulate ion fluxes in excitable cells.
Cell Mol Neurobiol 1988 Jun
PMID:Formation of second messengers in response to activation of ion channels in excitable cells. 245 43

BALB/MK is a nontransformed epithelial cell line derived from primary BALB/c mouse keratinocytes that requires epidermal growth factor (EGF) for growth. Using a defined-medium culture system, we investigated the role of physiological concentrations of EGF on phosphoinositide metabolism in these cells. The results show that EGF rapidly activates phospholipase-C mediated phosphoinositide metabolism resulting in the generation of the second messengers inositol 1,4,5-trisphosphate and diacylglycerol. These metabolites control intracellular Ca2+ levels and activate protein kinase C, respectively. Protein kinase C activation in response to EGF was evidenced by the phosphorylation of the acidic 80 kilodalton endogenous protein substrate (p80) specific for this kinase. In contrast, insulin, which acts in concert with EGF to cause BALB/MK cell proliferation, had no effect on phosphoinositide metabolism nor led to any additional stimulation when added in combination with EGF. Taken together, our results show that rapid alterations in phosphoinositide metabolism and protein kinase C activation are associated with the normal mitogenic response of keratinocytes to EGF.
Mol Endocrinol 1988 Sep
PMID:Epidermal growth factor activates phosphoinositide turnover and protein kinase C in BALB/MK keratinocytes. 245 6

The plc gene for phospholipase of Pseudomonas aeruginosa, able to be transcribed only from its own promoter, has been introduced into Escherichia coli, Pseudomonas aeruginosa and Pseudomonas putida cells in the recombinant plasmid pPMS21 of a wide host range. The expression of plc gene in all recipient cells has been shown to be phosphate regulated. The fact emphasizes the identity of pho-regulation systems in Escherichia coli and Pseudomonas cells. The level of phospholipase activity is similar in Pseudomonas putida and Pseudomonas aeruginosa under the conditions of the gene derepression, while in Escherichia coli cells the level does not exceed 10% of activity registered in Pseudomonas cells.
Mol Gen Mikrobiol Virusol 1989 Sep
PMID:[Expression of the phospholipase C gene of Pseudomonas aeruginosa in Escherichia coli and Pseudomonas]. 251 30

Trypanosoma brucei contains a membrane-bound phospholipase C which converts the variant surface glycoprotein (VSG), anchored in the membrane by a C-terminal glycosyl-phosphatidylinositol moiety, into a soluble form and diacylglycerol. The amino acid sequence (358 residues) of this enzyme, derived from the nucleotide sequence of the cDNA and the gene, reveals a polypeptide which lacks an obvious N-terminal signal sequence and stretches of exclusively hydrophobic residues. These properties suggest that the phospholipase is synthesized in the cytoplasm and subsequently associates with or translocates across intracellular membranes. There are much higher levels of glycosyl-phosphatidylinositol specific phospholipase C mRNA in bloodstream form than in procyclic form trypanosomes. The phospholipase gene is probably present in one or two copies per haploid genome, probably not associated with VSG expression sites.
Mol Biochem Parasitol 1989 Mar 15
PMID:Sequence and expression of the glycosyl-phosphatidylinositol-specific phospholipase C of Trypanosoma brucei. 252 22

Conditions have been established for the incorporation of [3H]inositol ([3H]Ins) into the phosphoinositides of cultured bovine adrenal zona fasciculata/reticularis (ZFR) cells. Stimulation of these prelabelled cells with angiotensin II (10(-11)-10(-7) M AII) resulted in the dose-dependent (max. 16-fold at 10(-7) M AII), time-dependent formation of water-soluble radiolabelled products which show the same chemical and chromatographic properties as [3H]InsP, [3H]InsP2 and [3H]InsP3 standards. The results of the time-course studies of the changes in these products are consistent with the view that AII rapidly (less than 15 s) induces the activation of a polyphosphoinositide-specific phospholipase C. The action of this phospholipase on the polyphosphoinositides is sustained throughout 15 min of stimulation. The dose dependency of this response correlates closely with cortisol output and is reduced (to 52%, P less than 0.00005), but not abolished, in the absence of extracellular Ca2+. To our knowledge these results are the first clear demonstration that AII stimulates a polyphosphoinositide-specific phospholipase C in bovine ZFR cells.
Mol Cell Endocrinol 1989 Jun
PMID:Angiotensin II-stimulated cortisol secretion is mediated by a hormone-sensitive phospholipase C in bovine adrenal fasciculata/reticularis cells. 254 75

We described that oxygen deprivation induced in cultures of heart muscle cells, biochemical events similar to those described in ischemic tissue: arachidonic acid liberation, loss of membrane phospholipids and increase in neutral lipids. Since glucocorticoids have been described to inhibit phospholipase activity and to exert beneficial effects during myocardial infarction, we studied in our experimental model the action of dexamethasone on the metabolism of arachidonic acid and on the synthesis of immunoreactive prostaglandins. Our results show that heart muscle cells produce prostaglandin E2 and 6-keto-prostaglandin-F1 alpha. This synthesis, inhibited by dexamethasone (70% inhibition), decreased after oxygen-deprivation (-45%). The effect of oxygen deprivation and dexamethasone (-60%) are not additive. Moreover, steroid treatment failed to counteract the loss of polyunsaturated fatty acids from the phospholipids, the increase in neutral lipids and the liberation of arachidonic acid induced by oxygen deprivation in muscle cells. These results may indicate that the cardiovascular effects of glucosteroids are not the consequence of a direct effect on heart metabolism at cellular level.
Mol Cell Biochem
PMID:Effect of glucocorticoids on arachidonic acid metabolism and prostaglandin secretion by cultures of newborn rat heart cells. 277 32

Increased breakdown of myocardial phospholipids to fatty acids and lysophosphoglycerides is an early feature of myocardial ischemic injury and many investigators believe that enhanced phospholipase action is an important factor in the process. Several recent reports indicate that inhibitors of phospholipase A, such as mepacrine, chloroquine and chlorpromazine, can prevent heart phosphoglyceride breakdown in vivo. We isolated the phospholipases A from rat heart cytosol and sarcoplasmic reticulum and examined the effects of various cardioprotective substances on their activity. Most of the cardioprotective agents studied inhibited the heart phospholipases in vitro, providing further evidence that phospholipid degradation in ischemic myocardial injury may be modulated by pharmacologic agents.
Mol Cell Biochem
PMID:Role of phospholipases in myocardial ischemia: effect of cardioprotective agents on the phospholipases A of heart cytosol and sarcoplasmic reticulum in vitro. 277 45


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