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

Both phosphatidylethanolamine(PE)-N-methylation and phosphatidyl-inositol bisphosphate (PI-bisphosphate) breakdown potentially modify the microdomains in the sarcolemmal lipid bilayer. In this study the possibility of a mutual interaction between the enzymes responsible for these phospholipid reactions is examined. In sarcolemma purified from rat heart, prior hydrolysis of PI lipids by exogenous specific phospholipase C inhibited (to 75, 59 and 78% of control for sites I, II and II, respectively) the PE-N-methyltransferase system. In cultured rat cardiomyocytes the addition of L-methionine, a precursor for the methyl donor S-adenosylmethionine, stimulated PE-N-methylation in a concentration (0.2-300 microM)-dependent manner. Methionine (50 microM) decreased the basal rate of PI-bisphosphate hydrolysis (to 72% of control), but had no effect on the phenylephrine-stimulated PI-bisphosphate hydrolysis. Maximal activation of the PI-bisphosphate breakdown by 30 microM phenylephrine did not affect the rate of PE-N-methylation in the presence of exogenous methionine (50 microM). These findings support the existence of interactions, although discrete, between the enzymes involved in the PE-N-methylation and PI turnover.
Mol Cell Biochem 1989 Oct 31
PMID:Discrete interactions between phosphatidylethanolamine-N-methylation and phosphatidylinositolbisphosphate hydrolysis in rat myocardium. 257 24

Biochemical events underlying neurotensin action at the pituitary were investigated in primary culture of anterior pituitary cells prelabeled with [3H]inositol. Incubation with the tridecapeptide produced a dose-dependent increase in the content of total [3H]inositol phosphates. The time-course showed that the effect was rapid and significant within 1 min. Fractionation of [3H]inositol phosphates revealed that inositol triphosphate (IP3) and inositol diphosphate (IP2) increased earlier than inositol monophosphate (IP1). Structure/activity correlation studies demonstrated the specificity of neurotensin effect, showing that acetylneurotensin(8-13) displayed an action similar to the natural peptide, while neurotensin(1-6) hexapeptide did not exhibit any effect. The neurotensin analog [D-Trp11]-neurotensin antagonized in a concentration-dependent manner the effect of neurotensin both on prolactin release and on [3H]inositol phosphate production. The loss of prelabeled phosphoinositides was also investigated. Phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) and phosphatidylinositol-4-phosphate (PtdIns-4-P) decreased significantly within 15 s, while a slight decline in phosphatidylinositol (PtdIns) level appeared only 1 min after neurotensin addition. These results suggest that neurotensin action at the pituitary is mediated by the early hydrolysis of polyphosphoinositides, leading to the production of 1,2-diacylglycerol and inositol phosphates which may initiate intracellular processes responsible for hormonal release.
Mol Cell Endocrinol 1985 Oct
PMID:Neurotensin stimulates polyphosphoinositide breakdown and prolactin release in anterior pituitary cells in culture. 299 63

Phosphatidylinositol 4,5-bisphosphate (PIP2) breakdown was stimulated by agonists acting at muscarinic cholinergic and alpha 1-adrenergic receptors in mouse brain. Ethanol, in vitro, inhibited basal cerebral cortical PIP2 breakdown with a threshold concentration of 75-100 mM. Basal PIP2 breakdown in hippocampus and striatum was less sensitive to ethanol. A high concentration of ethanol (500 mM) increased the EC50 for carbachol stimulation of PIP2 breakdown in all three brain areas, but had no effect on the EC50 for norepinephrine. Following chronic ingestion of ethanol by mice, the EC50 for carbachol stimulation of PIP2 breakdown in cortex was decreased, and there was no change in striatum. These effects were consistent with previously observed increases in quinuclidinylbenzilate (QNB) binding in cortex, but not striatum, of mice fed ethanol chronically. However, in hippocampus, where chronic ethanol ingestion had also induced an increase in QNB binding, the EC50 for carbachol stimulation of PIP2 breakdown was increased. Binding studies using the specific M1 muscarinic cholinergic receptor antagonist, pirenzepine, revealed that the number of pirenzepine-binding sites was increased in cortex, but not hippocampus (or striatum) of ethanol-fed mice. These results support the hypothesis that high affinity pirenzepine-binding sites are coupled to PIP2 breakdown in mouse cortex. The changes in cerebral cortex represent one of the first demonstrations of a functional correlate of a change in receptor density in ethanol-treated animals. Increased sensitivity to cholinergic agonists in cortex may contribute to particular signs of ethanol withdrawal.
Mol Pharmacol 1986 Jul
PMID:Acute and chronic effects of ethanol on receptor-mediated phosphatidylinositol 4,5-bisphosphate breakdown in mouse brain. 301 7

Leishmania donovani promastigotes contain intense tartrate-resistant cell surface acid phosphatase (ACP1) which blocks superoxide anion production by activated human neutrophils [A.T. Remaley et al. (1984) J. Biol. Chem, 259, 11173-11175]. An extensively purified preparation of ACP1 dephosphorylates several phosphoproteins which are phosphorylated at serine residues; these include: pyruvate kinase (Km 1.6 microM; Vmax 71.4 U (mg protein)-1), phosphorylase kinase (Km 0.076 microM; Vmax 5.4 U (mg protein)-1) and histones (Km 4.86 microM; Vmax 2.2 U (mg protein)-1). However, the specific activity of the leishmanial phosphatase on these phosphoproteins is very low as compared to other phosphoprotein phosphatases. The phosphatase activity of ACP1 was also low on phosphohistone phosphorylated at tyrosine residues. Phosphatidylinositol-4,5-diphosphate (PIP2) and inositoltriphosphate (IP3) were also tested as ACP1 substrates. PIP2 was hydrolyzed rapidly by ACP1. The rate of hydrolysis of PIP2 was higher at pH 6.8 (Km 2.35 microM; Vmax 107 X 10(3) U (mg protein)-1) than at pH 5.5 (Km 4.16 microM; Vmax 71 X 10(3) U (mg protein)-1). 32P-labeled IP3 was also a substrate for ACP1; the hydrolysis products consisted of a mixture of inositoldiphosphate and inositolmonophosphate. ACP1 and ten other phosphatases were tested for their ability to dephosphorylate proteins and to inhibit O2- production by stimulated human neutrophils. There was no correlation between the protein phosphatase activity of the acid- and alkaline phosphatases and their ability to block neutrophil O2- production. The results indicate that ACP1 probably blocks the production of reduced oxygen intermediates by a mechanism that does not involve dephosphorylation of phosphoproteins; however, the possibility that the parasite's phosphatase affects phagocyte metabolism by degrading PIP2 or IP3 should be considered.
Mol Biochem Parasitol 1986 Aug
PMID:Hydrolysis of phosphoproteins and inositol phosphates by cell surface phosphatase of Leishmania donovani. 301 59

The various subtypes of adrenergic receptors represent distinct structural entities which are coupled in different ways to two major transmembrane signalling systems, the adenylate cyclase and phosphatidyl-inositol pathways. Recent evidence suggests that the functional linkage of both beta and alpha 1-adrenergic receptors to their respective effector systems is regulated by covalent modification of the receptors by phosphorylation-dephosphorylation reactions. Receptor phosphorylation appears to lead to desensitization of the biological response to receptor stimulation. Several kinases including protein kinase A, protein kinase C and a cAMP independent kinase appear to participate in these reactions.
J Mol Cell Cardiol 1986 Sep
PMID:Ciba-Geigy award for outstanding research. Regulation of adrenergic receptor function by phosphorylation. 302 44

Twenty-six days of fat deficiency brought about a decrease of linoleic and an increase of oleic acid in rough endoplasmic reticulum (RER) of guinea pig liver. Arachidonic acid was only slightly decreased in some phospholipids whereas eicose-5,8,11-trienoic acid was not enhanced except in phosphatidyl-inositol. All these changes were relevant specifically in phosphatidylinositol molecules and less important in phosphatidylcholine and phosphatidylethanolamine. Fat deficiency did not modify the relative proportion of phospholipids and cholesterol. Therefore, fat deficient guinea pig microsomes are a good model to study the effect of unsaturated fatty acids on membrane properties. Fluorescent anisotropy of RER membranes, lipids and phospholipids labeled with diphenylhexatriene, was increased by the fat deficiency. The most important increase was observed in liposomes of a mixture of RER phosphatidylinositol, phosphatidylserine and sphingomyelin. A small change was found in phosphatidylcholine and phosphatidylethanolamine dispersions at 37 degrees C. The modification of the lipid unsaturation evoked fluorescent anisotropy changes. Temperature-dependent fluorescent polarization curves of RER membranes labeled with trans-parinaric acid did not show inflections in the temperature range from 5 to 45 degrees C but, RER lipids and phospholipids presented a phase separation at about 20 degrees C. This inflection point was not modified by the fat deficient diet. In those liposomes prepared with a mixture of RER phosphatidylinositol, phosphatidylserine and sphingomyelin, the inflection point was produced at about 37 degrees C.
Mol Cell Biochem 1987 Dec
PMID:Effects of fatty acid deficiency on the lipid composition and physical properties of guinea pig rough endoplasmic reticulum. 344 Dec 50

The regulation of phosphatidylinositol turnover by alpha-adrenergic agonists in rat parotid acinar cell aggregates was examined with respect to kinetics and agonist-antagonist interactions. Phosphatidylinositol turnover was followed by the changes in the specific activities of [32P]phosphatidic acid and [32P]phosphatidylinositol. The specific activity of phosphatidic acid increased rapidly (within 1 min) after addition of epinephrine (10(-5) M), reached a maximal level within 12-16 min, and then decreased. Incorporation of 32P into phosphatidylinositol exhibited a lag phase of about 5 min and then increased continuously for an additional 40 min. The absolute amounts of phosphatidic acid and phosphatidylinositol did not change. The concentrations of epinephrine needed to stimulate 32P incorporation into phosphatidic acid and phosphatidylinositol, measured at 15 and 30 min, respectively, were similar; Ka values of 2.05 +/- 0.46 X 10(-6) M for phosphatidic acid and 2.98 +/- 0.30 X 10(-6) M for phosphatidylinositol were found. The effects of agonists on 32P labeling of phosphatidylinositol, in order of potency, were epinephrine greater than or equal to norepinephrine greater than phenylephrine much greater than normetanephrine. When various adrenergic antagonists were evaluated for their ability to inhibit 10(-5) M epinephrine-stimulated 32P incorporation into both phosphatidic acid and phosphatidylinositol, the order of antagonist potency was prazosin greater than or equal to phenoxybenzamine greater than phentolamine greater than or equal to yohimbine greater than much greater than propranolol. These findings indicate that phosphatidylinositol-phosphatidic acid turnover in the rat parotid gland is mediated by the alpha 1-adrenergic receptor system.
Mol Pharmacol 1982 Jan
PMID:Alpha1-adrenergic stimulation of phosphatidylinositol-phosphatidic acid turnover in rat parotid cells. 612 17

The incorporation of myo-[2-3H]inositol into phosphatidylinositol of the aorta and the vas deferens was measured and the effects of Ca2+ and other divalent cations were determined. When incubated in normal Krebs-Ringer buffer, only negligible radioactivity was incorporated into aorta slices. Mn2+ increased the incorporation greatly. The enhanced incorporation was attributable to an increase in CDP-diglyceride:inositol transferase activity, rather than the myo-inositol exchange reaction. Transferase activity was increased 20-fold by 1 mM Mn2+, in the presence of 20 mM Mg2+. The Mn2+-stimulated activity was strongly inhibited by Ca2+. In the absence of Mn2+, but presence of 20 mM Mg2+, transferase activity was inhibited 80% by 0.01 mM Ca2+. Removal of endogenous Ca2+ from the tissue by ionophore A23187 and EGTA increased the incorporation of myo-[2-3H]inositol into phosphatidylinositol. These findings indicate that Ca2+ inhibited the synthesis of phosphatidylinositol. The proposed action of cholinergic and alpha-adrenergic agonists in enhancing the degradation and turnover of phosphatidyl-inositol and in provoking the influx of Ca2+ should be unfavorable to the recovery of cellular phosphatidylinositol content.
Mol Cell Endocrinol 1981 Jan
PMID:Inhibition by Ca2+ of the incorporation of myo-inositol into phosphatidylinositol. 625 1

The effects of luteinizing hormone-releasing hormone (LHRH) and human pancreatic growth hormone-releasing factor (hpGRF(1-40)-NH2) on phospholipid metabolism were studied in rat anterior pituitary cells in primary culture. In a 4-fold enriched population of gonadotrophs, 30 nM LHRH increased 32Pi incorporation into phosphatidic acid (PA) as early as 1 min after its addition. Phosphatidylinositol (PI) labeling was increased 1 min later. The stimulatory action of LHRH was observed in both phospholipids up to 100 min, the last time interval studied. The decapeptide did not affect 32Pi labeling of phosphatidylcholine (PC), lysoPC, phosphatidylethanolamine or phosphatidylserine. Dose-response studies performed after 25 min of incubation showed an ED50 value of LHRH action at approximately 1 nM for PI labeling. In contrast, the addition of 0.1 microM GRF to anterior pituitary cells enhanced 32Pi incorporation only into PC after a 60 min incubation period. The present data suggest that stimulation of acidic phospholipid metabolism, particularly an increase in PA-PI turnover, may represent an early event in the mechanism of action of LHRH but not GRF in the anterior pituitary gland.
Mol Cell Endocrinol 1984 Jul
PMID:LHRH rapidly stimulates phosphatidylinositol metabolism in enriched gonadotrophs. 643 3

Phosphatidylinositol (PtdIns) turnover in murine atria is stimulated by the cholinergic agonist carbachol. Incorporation of either [32P]phosphate or [myo-3H]inositol into PtdIns is increased 40-80% by 30 microM carbachol, but carbachol does not increase the labeling of other major phospholipids. Cholinergic stimulation of PtdIns synthesis is blocked by the muscarinic antagonist atropine. When Ca2+ is removed from the extracellular medium, there is a large increase in basal PtdIns synthesis, and carbachol does not produce any further increase in [32P]phosphate incorporation. Carbachol also stimulates hydrolysis of phosphoinositides as measured by myo[3H]inositol 1-phosphate accumulation. A maximal concentration of carbachol causes a 300-400% increase in phosphoinositide breakdown, and half-maximal stimulation occurs at a carbachol concentration of approximately 10 microM. Muscarinic stimulation of inositol phospholipid hydrolysis is seen in left and right atria as well as in ventricular tissue. The effect of carbachol on phosphoinositide hydrolysis is markedly attenuated when extracellular Ca2+ is removed. In contrast to most other hormone receptors linked to PtdIns metabolism, there is no evidence that cardiac muscarinic receptors mediate their physiological effects through Ca2+ mobilization. Thus, receptor-mediated changes in PtdIns turnover may serve a different function in the heart than in hormone-receptor systems that utilize Ca2+ as a second messenger.
Mol Pharmacol 1983 Nov
PMID:Muscarinic stimulation of phosphatidylinositol metabolism in atria. 663 1


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