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)

Renin-angiotensin (RA) system plays an important role in cardiovascular homeostasis. Here, we have described the recent progress in our study of renin release as well as the cellular action of angiotensin II. (1) Microdissection of an isolated afferent artery with or without macula densa (MD) has revealed that renin release is regulated by NaCl exposure to MD. Furosemide, prostaglandins (PGE2 and PGI2) and adenosine modulate its function. (2) Angiotensin (ang) II increases cytosolic free calcium and induces the formation of inositolphosphates in vascular smooth muscle cells. Deduced protein structure of ang II receptor (AT1-R) cDNA has indicated the presumed link of AT1-R with phospholipase C. Through the cellular action, ang II has been reported to regulate gene expression.
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PMID:[Mechanism of renin release and cellular action of angiotensin II]. 129 35

In the kidney, adenosine plays important regulatory roles, including renal blood flow, glomerular filtration rate, renin secretion, tubuloglomerular feedback, tubular reabsorption of sodium and water, sympathetic neurotransmitter release, and erythropoietin secretion. These functions are mediated through adenosine 1 (A1)-receptors and adenosine 2 (A2)-receptors. These receptors couple to the inhibition and stimulation of adenylate cyclase, through Gi and Gs proteins, respectively. A variety of other effecter systems have been reported to be coupled to A1 receptors, including phospholipase C, phospholipase A2 and potassium, as well as Ca++ channels. Recently, A1 receptors, A2 receptors and novel A2 receptor have been cloned, sequenced and expressed. In association with the development of selective adenosine analogues, we are now ready to take up problems at the biochemical and molecular biological levels.
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PMID:[Adenosine and adenosine receptors in the kidney]. 149 49

NG108-15 cells, a neurally derived clonal cell line, express various components of the renin-angiotensin system and thus serve as a model of the cellular action of angiotensin (Ang) II. NG108-15 cells contain a high-affinity binding site for Ang II, with a Kd of 1.1 nM and a Bmax of 6.5 fmol/mg protein. Ang peptides competed for 125I-Ang II binding with an order of potency of Ang II greater than Ang-(2-8) much greater than Ang-(1-7). The subtype 1 (or B)-selective Ang II receptor antagonist DuP 753 as well as [Sar1,Ile8]Ang II and [Sar1,Thr8]Ang II competed for Ang II binding with high affinity, whereas the subtype 2 (or A)-selective Ang receptor antagonist CGP 42112A was partially effective only at a 300-fold higher concentration. When NG108-15 cells were induced to differentiate by treatment with dibutyryl cyclic adenosine 3',5'-monophosphate, the density of Ang II receptors increased dramatically, with little change in affinity (1.1 versus 4.2 nM) or competition by Ang peptides. In marked contrast to undifferentiated cells, CGP 42112A became a potent competitor (IC50, 1 nM) for the majority (90-95%) of Ang II binding, whereas DuP 753 competed for only 5-10% of the binding sites. Ang II caused a dose-dependent mobilization of cytosolic Ca2+ in undifferentiated NG108-15 cells through activation of phospholipase C and the production of inositol 1,4,5-trisphosphate. In these cells, Ca2+ mobilization was blocked by either DuP 753 or the sarcosine Ang II analogues, whereas CGP 42112A was ineffective. Ang II also mobilized intracellular Ca2+ in differentiated NG108-15 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Identification and regulation of angiotensin II receptor subtypes on NG108-15 cells. 204 60

Endothelin, a 17-DKa peptide originally described as a potent vasoconstrictor, also stimulates the release of important regulators of glomerular hemodynamics such as atrial natriuretic factor and renin. In the present study we investigated the role of endothelin in the release of another potent vasoconstrictor and mitogen of human mesangial cells, the platelet-derived growth factor. Endothelin stimulated PDGF release at 12 hours and the effect was sustained for 36 hours. This effect was associated with the enhanced induction of mRNAs encoding PDGF A- and B-chain. Endothelin also induced mitogenesis in human mesangial cells which was accompanied by activation of phospholipase C with increased inositol phosphate turnover. These data suggest a mechanism by which endothelin may regulate mesangial cell function in disease states.
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PMID:Endothelin stimulates PDGF secretion in cultured human mesangial cells. 207 61

The present study was designed to study the functional properties of Angiotensin II (Ang II) binding sites in vascular smooth muscle cells in the Milan hypertensive rat (MHS), a model of low renin hypertension. Smooth muscle cells from MHS rats exhibited increased growth in culture in comparison with the Milan normotensive strain (MNS) as determined by population doubling times (24.5 +/- 2 and 34.8 +/- 2 hours, n = 4, respectively). Hormone receptor number, evaluated by binding assays using [125I]Ang II, showed no difference in either receptor number or affinity for both cell types. The functional responsiveness of Ang II receptors was evaluated by measuring the activation of phospholipase C, Na(+)-H+ exchange, and cytosolic Ca2+ levels. Phospholipase C activity was determined as tritium-labeled inositol trisphosphate and bisphosphate release before and after 15-second exposure to 10(-7) M Ang II. Ang II-stimulated phospholipase C activity in MNS (p less than 0.02) but not in MHS cells. Na(+)-H+ exchange was measured as the dimethylamiloride-sensitive 22Na+ influx into acid-loaded vascular smooth muscle cells with and without 10(-7) M Ang II. In MNS cells, Ang II significantly stimulated (p less than 0.001) antiporter activity but not in MHS cells, which showed a uniformly blunted response. MHS cells exhibited higher basal cytosolic Ca2+ levels than MNS cells, but Ca2+ rapidly increased in the presence of Ang II in MNS but not in MHS cells. Direct activation of phospholipase C by GTP-gamma-S in permeabilized cells indicated that both strains exhibited similar coupling levels by guanine-nucleotide binding proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vascular smooth muscle cells from the Milan hypertensive rat exhibit decreased functional angiotensin II receptors. 234 21

Acetylglyceryl ether phosphorylcholine (AGEPC), commonly known as platelet activating factor, was found to strongly inhibit renin secretion in cultures rich in juxtaglomerular cells. This inhibitory action of AGEPC was accompanied by an enhanced calcium permeability of the cell membrane as evaluated from measurements of the uptake of 45Ca. Simultaneous addition of the calcium channel blocker verapamil abolished the effects of AGEPC on both renin secretion and calcium permeability. Furthermore, addition of AGEPC to the cell cultures led to a decrease of 32P-labeled phosphatidylinositol 4,5-bisphosphate and to an increase in 3H-labeled diacylglycerol, indicating an activation of phospholipase C by AGEPC.
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PMID:Inhibition of renin secretion by platelet activating factor (acetylglyceryl ether phosphorylcholine) in cultured rat renal juxtaglomerular cells. 298 64

It was the aim of the present study to get insight into some of the intracellular mechanisms by which the vasoconstrictor hormones angiotensin II (ANG II), arginine vasopressin (AVP), and norepinephrine (NE) inhibit renin release from renal juxtaglomerular cells. To this end a primary cell culture from rat renal cortex was established that consisted of 50% juxtaglomerular cells. The cultured juxtaglomerular cells contained prominent renin granules closely resembling those in the intact kidney and responded to a number of stimuli of renin release. By using these cultures, we found that ANG II (10(-7) M), AVP (10(-6) M), and NE (10(-5) M) inhibited renin release and increased the calcium permeability of the plasma membrane of the cultured cells. Both the effects on renin release and on calcium permeability could be diminished or even be abolished by the calcium channel blocker verapamil (Vp) (10(-5) M). ANG II, AVP, and NE led to an increased formation of diacylglycerol (DAG), a well-known stimulator of protein kinase C (PKC). Moreover, a direct stimulation of PKC by 12-O-tetradecanoylphorbol-13-acetate (TPA) (10(-8)-10(-6) M) also inhibited renin release and increased the calcium permeability of the cell membrane. Similar to ANG II, AVP, and NE, the effects of TPA on calcium permeability and renin release could be diminished by Vp. In conclusion, these results point toward a common mechanism by which vasoconstrictors inhibit renin release from renal juxtaglomerular cells: ANG II, AVP, and NE activate a phospholipase C, which generates DAG.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of protein kinase C in inhibition of renin release caused by vasoconstrictors. 300 66

This study was performed to examine the effects of endothelin (ET)-1, ET-2, and ET-3 on renin secretion from cultured mouse renal juxtaglomerular (JG) cells. Although different ETs had no consistent effect on basal renin secretion, they equipotently inhibited adenosine 3',5'-cyclic monophosphate (cAMP)-stimulated renin release with a concentration of approximately 3 nM inhibiting 50% of maximal response. ETs did not significantly affect renin release stimulated by the nitric oxide donor sodium nitroprusside (100 microM) or that stimulated by low [2 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] or high (3 mM CaCl2) extracellular calcium. The inhibitory effect of ETs on cAMP-dependent renin secretion was abolished by lowering extracellular calcium concentration to the nanomolar range. However, the action of ETs was not changed by the ETA receptor antagonist BQ-123 (100 nM) and was mimicked by ETB receptor agonists IRL-1620 (1 microM), sarafotoxin S6b (1 microM), and [Ala1,3,11,15]ET-1 (1 microM). All ETs induced calcium oscillations in JG cells that were dependent on extracellular calcium and were associated with prominent calcium-activated chloride currents. These findings suggest that ETs inhibit rather selectively the cAMP-activated pathway of renin secretion through a calcium-sensitive process. The action of ETs on renal JG cells appears to be mediated via ETB receptors and is presumably related to activation of phospholipase C and subsequent events.
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PMID:Effects of endothelins on renin secretion from isolated mouse renal juxtaglomerular cells. 784 Feb 46

SHR (spontaneously hypertensive rat) is the most popular genetic hypertensive model rat. Using the F2 progeny obtained from SHR and normotensive rats, for example, WKY (Wistar-Kyoto rat), many cosegregation studies to find the genes responsible for blood pressure have been done. In this review, we present some studies using F2 rats concerning candidate genes, renin, kallikrein, sodium potassium-ATPase, heat shock protein 70, angiotensin converting enzyme, phospholipase C-delta 1 and SA gene to show whether these genes really associate with blood pressure. We discuss the signification of these genes in the process of producing SHR and stroke-prone SHR from WKY. We hope these studies will lead to identify the mechanism of human essential hypertension.
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PMID:[Cosegregation studies in spontaneously hypertensive rats]. 832 Aug 40

The present study was performed to determine whether transforming growth factor beta 1 (TGF beta 1) and tissue renin-angiotensin (R-A) system are involved in hypertrophic cardiomyopathy. Cardiomyopathic Syrian hamsters (Bio 14.6) aged 4 and 20 weeks were used as a model of hypertrophic cardiomyopathy and compared with age-matched F1 beta Syrian hamsters. Total RNA was extracted from the left ventricle, and the m-RNA expressions of TGF beta 1 and angiotensinogen (ATN) were examined by Northern blotting or Ribonuclease Protection Assay (RPA). The activity of angiotensin-converting enzyme (ACE) was assayed by the modified method of Tess, using crude membrane fraction prepared from left ventricle. The effect of angiotensin II (A II) on phosphatidylinositol (PI) metabolism was evaluated by the PI -or PIP2 (phosphatidylinositol 4,5-bis phosphate)-specific phospholipase C (PLC), which releases inositol-1,4,5-triphosphate (I P3) and diacylglycerol (DAG) in cardiac myocytes. The m-RNA expressions of TGF beta 1 and ATN were detected in each group of Syrian hamsters (BIO14.6 and F1 beta). TGF beta 1 m-RNA expression was markedly increased in BIO14.6 compared with F1 beta at the age of 4 weeks, and was more intensified at the age of 20 weeks, while no significant difference was demonstrated in the ATN m-RNA expression. ACE activity in the left ventricle was enhanced in 20 week-old BIO14.6 compared with age-matched F1 beta. The activities of PI- and PIP2-specific PLC were enhanced in 20 week-old BIO14.6 in response to A II stimulation. DAG and IP3, which are second messengers and activate protein kinase C. were significantly released from the cardiac myocytes of 20 week-old BIO14.6. These results suggest that the increase in expression of TGF beta 1 gene in the left ventricle may induce cardiac hypertrophy in BIO14.6, and that the exaggerated response of phosphatidylinositol metabolism to A II and the increased activity of ACE in cardiac tissue R-A system may lead to the development of cardiac hypertrophy.
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PMID:[Tissue factors contributing to cardiac hypertrophy in cardiomyopathic hamsters (BIO14.6): involvement of transforming growth factor-beta 1 and tissue renin-angiotensin system in the progression of cardiac hypertrophy]. 838 86


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