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)

In rat liver prostaglandin F2 alpha (PGF2 alpha) and thromboxane A2 (TXA2), released from non-parenchymal cells, have been implicated as mediators of the enhancement of glucose and lactate output from parenchymal cells caused by sympathetic nerve stimulation [Iwai, M. et al. (1988) Eur. J. Biochem. 175, 45-50]. In isolated rat hepatocytes PGF2 alpha, of which 75% were degraded within 10 min, but not the TXA2 analogue U46619 increased inositol 1,4,5-trisphosphate (IP3), glycogen phosphorylase a activity and glucose output like noradrenaline and vasopressin; cyclic AMP remained unaltered. The maximal increase in IP3 was reached within 20 s and in phosphorylase activity as well as glucose release within 1 min. The results indicate that only PGF2 alpha but not TXA2 can play a role as a direct mediator of the sympathetic metabolic nerve actions in rat liver and that hepatocytes contain also stimulatory prostaglandin receptors linked to phospholipase C in addition to the inhibitory receptors linked to adenylate cyclase known thus far.
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PMID:Direct activation by prostaglandin F2 alpha but not thromboxane A2 of glycogenolysis via an increase in inositol 1,4,5-trisphosphate in rat hepatocytes. 255 Dec 82

In the rat brain, a number of receptors are linked to phospholipase C which catalyzes the hydrolysis of membrane inositol phospholipids; stimulation of alpha 1-adrenergic receptors, for example, increases polyphosphoinositide turnover, but stimulation of alpha 2-receptors does not. The hydrolysis of inositol phospholipids in rat cortical slices was investigated using a direct assay involving prelabeling these lipids with 3H-inositol and then measuring the formation of 3H-inositol phosphates in the presence of lithium ions. As expected, clonidine, an alpha 2-agonist, did not stimulate the formation of 3H-inositol phosphates; however, clonidine antagonized the ability of noradrenaline to stimulate 3H-inositol phosphate formation. This effect was not blocked by antagonists of alpha 2, 5HT2, H2, or muscarinic receptors. Clonidine did not affect carbachol-stimulated 3H-inositol phosphate formation.
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PMID:Inhibition of polyphosphoinositide turnover in rat cerebral cortex by clonidine. 255 43

Small branches from the superior mesenteric arteries (100-200 microns outer diameter) freshly dissected from male Wistar-Kyoto (WKY) rats were mounted for tension recordings. Some arterial rings were left in physiological salt solution and used as intact arteries while others were made permeable with alpha-toxin and incubated in cytoplasmic substitution solution. The relationship between ambient [Ca2+] and tension development during various modes of activation was measured in both intact and permeable arterial rings. The effects of ryanodine and 12-O-tetradecanoyl phorbol-13-acetate (TPA) were tested. Ryanodine had no effect on the tone developed in response to noradrenaline, but tension was increased when the tissues were bathed in 80 mmol/l K+ and [Ca2+] was raised (10 mmol/l). If it is assumed that ryanodine acts exclusively to enhance the permeability of the sarcoplasmic reticulum in smooth muscle, these data suggest that noradrenaline-induced tone is partly due to inhibition of Ca2+ buffering in the sarcoplasmic reticulum. However, this action of noradrenaline is not as pronounced in the resistance arteries as it is in the rabbit aorta. 12-O-tetradecanoyl phorbol-13-acetate had no effect on the noradrenaline-induced contractions of the intact resistance arteries, but caused a large leftward shift in the relationship between tension and extracellular [Ca2+] when high-K+ depolarization was the stimulus. This increased sensitivity to extracellular [Ca2+] could not be explained by stimulation of the Ca2+ influx. Instead, application of TPA to the rings made permeable with alpha-toxin dramatically increased the myofilament sensitivity to Ca2+, as demonstrated by a shift to the left of the tension-intracellular-[Ca2+] curve.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Receptor-mediated C-kinase activation contributes to alpha-adrenergic tone in rat mesenteric resistance artery. 255 98

In rat striatal slices, 2-chloroadenosine, which had no direct effect on inositol phosphate formation, potentiated in a dose-dependent manner the accumulation of inositol phosphates induced either by carbamylcholine (10(-3) M) or by noradrenaline (10(-4) M). Experiments made on pure populations of striatal neurons or striatal glial cells in primary culture from mouse embryos indicated that 2-chloroadenosine potentiated the noradrenaline-elicited phosphoinositide breakdown in striatal glial cultures but did not modify the responses evoked either by noradrenaline or by carbamylcholine in striatal neuronal cultures. However, 2-chloroadenosine enhanced both the carbamylcholine and the noradrenaline-induced accumulation of inositol phosphates in neuroglial cocultures just as it did in rat striatal slices. The potentiation by 2-chloroadenosine of the carbamylcholine response, which is neuron specific, involved a cooperative effect between neurons and glial cells and, as shown by additional experiments, required a brief contact only between the 2 types of cells. The potentiating effect of 2-chloroadenosine was blocked completely by a nonselective A1, A2 adenosine antagonist isobutylmethylxanthine either on rat striatal slices or on mouse embryonic cocultures (noradrenaline and carbamylcholine responses) or on mouse embryonic glial cultures (noradrenaline response). These data indicate the involvement of an extracellular membrane-bound adenosine receptor, possibly of the A1 subtype since N6-cyclohexyladenosine, an A1 adenosine receptor agonist, was more efficient than 5'-N-ethylcarboxamide-adenosine, a rather selective A2 adenosine receptor agonist. We propose that 2-chloroadenosine acts through an adenosine receptor located on glial cells and induces the synthesis of a substance that improves the coupling between carbamylcholine or noradrenaline and phospholipase C located in glial cells or neurons.
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PMID:A neuroglial cooperativity is required for the potentiation by 2-chloroadenosine of the muscarinic-sensitive phospholipase C in the striatum. 265 33

Previous experiments gave biochemical and electrophysiological evidence for the presence of functional V1-vasopressin receptors coupled to inositol lipid metabolism, but not to cyclic AMP accumulation in the rat superior cervical ganglion. This work was designed to investigate whether there was an action of vasopressin on the noradrenaline-induced cyclic AMP accumulation through the activation of phospholipase C. Our results clearly demonstrate that arginine-vasopressin potentiates cyclic AMP accumulation induced by noradrenaline or isoproterenol in a concentration-dependent manner. The potentiation was unaffected by phentolamine, but was suppressed by the V1-type vasopressin receptor antagonists. Moreover, the phorbol ester 4 beta-phorbol-12-myristate-13-acetate (TPA) did not affect this potentiation which seemed to be Ca2+-dependent. The results suggest that vasopressin may modulate the activity of autonomous functions in the sympathetic ganglia.
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PMID:Vasopressin potentiates the noradrenaline-induced accumulation of cyclic AMP in the rat superior cervical ganglion. 283 95

Naloxone (10(-5) -10(-9) M) significantly increased the K+ (30 mM)-induced release of [3H[noradrenaline when it was applied to cortical slices taken from morphine-dependent rats but did not change the release of transmitter when applied to slices prepared from non-dependent animals. Therefore, this preparation was considered suitable to study withdrawal-related events and was used to monitor the agonist-induced changes of phospholipase C activity in the withdrawal state. Noradrenaline (1-100 microM) and carbachol (50-500 microM), when applied to cortical slices preincubated with [3H]inositol or with [32P]orthophosphate, dose dependently increased the formation of labeled inositol phosphates or of phosphatidic acid. This confirmed that noradrenaline and carbachol increase phospholipase C activity. This increase was significantly enhanced by naloxone (10(-6) M) when the slices were taken from dependent animals. The results now reported show for the first time in mammalian tissues that opioid withdrawal is associated with changes of phosphoinositide metabolism.
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PMID:Morphine withdrawal in vitro: potentiation of agonist-dependent polyphosphoinositide breakdown. 284 65

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

The most common haemodynamic abnormality in human essential hypertension is an increase in systemic vascular resistance. Morphologic substrate for increased flow resistance is a narrowing of the lumen of arteriolar resistance vessels. During the course of essential hypertension, this is associated with an increase in wall (mainly media) thickness due to hypertrophy and hyperplasia of vascular smooth muscle cells. In contrast to concepts interpreting media thickening strictly as structural adaptation to increased perfusion pressure, various lines of evidence also point to pressure independent factors. In this context, extracellular factors such as "growth factors" as well as alterations in the activity of intracellular messenger systems must be considered. Recent studies suggest that substances generally known to act as vasoconstrictors such as angiotensin II, noradrenaline and arginine-vasopressin may also stimulate vascular smooth muscle cell growth and proliferation. Intracellular messenger systems with possible significance in the response to trophins and/or mitogens of vascular smooth muscle cells are phospholipase C, protein kinase C and the Na+/H+-antiport. These systems have been demonstrated to be altered in hypertension supporting the concept that one endogenous factor in human essential hypertension with pathophysiological significance, at least in a subgroup of patients, may be an enhanced reactivity of vascular smooth muscle cells to trophic and mitogenic stimuli. In this context, intracellular messenger systems such as phospholipase C, protein kinase C and/or the Na+/H+-antiport may play an important pathophysiological role.
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PMID:[Mechanism and significance of arteriolar media hypertrophy/ hyperplasia in arterial hypertension. Role of the Na+/H+ antiport]. 285 Apr 7

1. The apparent Ki values of (-)-noradrenaline (NA), (+)- and (-)-adrenaline (Ad), phenylephrine and the mono-fluorinated NAs (in position 2, 5 or 6) for alpha 1-adrenoceptors of intact BC3H1 cells labelled with [3H]-prazosin were greatly dependent on the incubation temperature. 2. The EC50 values of these compounds for stimulation of the inositol phosphate (IP) accumulation at 37 degrees C were intermediate between their apparent dissociation constants at 2 degrees C (Ki2 degrees) and at 37 degrees C (Ki37 degrees). 3. The fact that an irreversible blockade of 46% +/- 6% (n = 3) of the [3H]-prazosin binding sites by phenoxybenzamine reduced the maximal IP-formation induced by NA by 57% +/- 5% (n = 3) shows that there is a direct coupling between alpha 1-adrenoceptors and phospholipase C in BC3H1 cells. 4. The Ki37 degrees s of all agonists tested were in the same range (0.1 to 1 mM) and showed no simple correlation with their EC50 values. 5. The Ki2 degrees values for all the agonist correlated linearly with their EC50 values but were about 20-100 times lower than the respective EC50 values (except for the partial agonist methoxamine). In order to explain this difference, we propose that the apparent high affinity in the cold could be due to an [3H]-prazosin-induced alteration of the active site of the alpha 1-adrenoceptor, increasing its apparent affinity for catecholamines.
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PMID:Complex interactions of agonists with alpha 1-adrenoceptors in intact cells. 290 9

Activation of alpha 1-adrenergic receptors increases [Ca+2]i and phosphatidylinositol phosphodiesterase (phospholipase C) activity in the pinealocyte. In this report the receptor involved in the stimulation of phospholipase C activity was further characterized, and the role of Ca2+ in this effect was investigated in some detail. Phospholipase C activity was estimated by measuring the production of [3H]inositol phosphates by [3H]inositol-labelled dispersed pinealocytes in suspension culture. Norepinephrine stimulated [3H]inositol monophosphate production severalfold; this was blocked by alpha 1-adrenergic antagonists, including prazosin, WB 4101, and phenoxybenzamine, but by neither an alpha 2- nor a beta-adrenergic antagonist, confirming that an alpha 1-adrenoceptor is involved in the regulation of phosphatidylinositol hydrolysis. Treatment with the Ca2+ chelator, EGTA, or with inorganic Ca2+ blockers, including Co2+, Mn2+, and La3+, reduced the norepinephrine-stimulated response, suggesting that the alpha 1-adrenergic stimulation of phospholipase C activity is Ca2+ dependent. However, phospholipase C activity was not increased by elevating intracellular Ca2+ with either the Ca2+ ionophore A23187 or with depolarizing concentrations of K+. These results indicate that although Ca2+ is necessary for alpha 1-adrenergic stimulation of phospholipase C activity, an increase in [Ca2+]i alone is not sufficient to stimulate the activity of this enzyme, and that effects which A23187 and depolarizing concentrations of K+ have on pineal function probably do not involve stimulation of phospholipase C activity.
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PMID:Permissive role of calcium in alpha 1-adrenergic stimulation of pineal phosphatidylinositol phosphodiesterase (phospholipase C) activity. 290 66


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