Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma renin activity and aldosterone concentrations were measured simultaneously with urinary excretion of kallikrein and four prostaglandins (PGE2, PGF2 alpha, 6 keto PFG1 alpha and TXB2) in 23 patients with pregnancy induced hypertension (17 with permanent PIH and six with labile PIH, since in these latter their hypertension was controlled only by home bed rest) and in 16 normotensive pregnant women at the same stage of gestation (31 +/- 3 weeks). PRA was lower in permanent PIH than in controls and in labile PIH. No difference between the three groups was observed for plasma aldosterone and the urinary excretion of kallikrein and of the prostaglandins except that TXB2 was higher in labile PIH than in permanent PIH. Correlation studies of kallikrein disclosed correlations with most prostaglandin excretions, explained by the physiological stimulation of phospholipase A2 by kallidin. Correlation studies of PRA disclosed unexpected negative correlation with PGE2 and 6 keto PGF1 alpha in the permanent PIH group. In conclusion, labile PIH has a different biological profile than permanent PIH since they have higher PRA and higher TXB2 excretion, an association which suggests a more pronounced ureteral compression by the gravid uterus in this group. Permanent PIH has a disregulation of the renin angiotensin-prostacyclin loop since PRA and 6 keto PGF1 are negatively correlated. This suggests the role of an independent vasopressive substance which would stimulate PGI2 and suppress renin secretion.
 ...
PMID:Renin angiotensin aldosterone system, urinary prostaglandins and kallikrein in pregnancy induced hypertension. Evidence for a disregulation of the renin-angiotensin-prostacyclin loop. 384 87

Prostaglandins and thromboxanes are 20-carbon-atom-chain fatty acids which contain a cyclopentane or oxane nucleus respectively. They belong to a family of icosanoids whose main intracellular precursor is arachidonic acid. These icosanoids are synthetized in all tissues (except red cells). Enzymatic hydrolysis of the arachidonic acid of lipids is the first step of their biosynthesis. This step, which is limitative, is usually catalyzed by phospholipase A2 and may be indirectly inhibited by glucocorticoids. Once released, arachidonic acid is promptly transformed into an endoperoxide intermediary through the action of an enzymatic complex called "cyclooxygenase". This intermediary is the precursor of both prostaglandins and thromboxane. Non-steroidal antiinflammatory agents such as acetylsalicylic acid and indomethacin have an inhibitory action on cyclooxygenase. The mechanisms of action of prostaglandins and thromboxane are still poorly understood. In certain tissues (platelets, adipose cells) their effect seems to involve stimulation of adenyl-cyclase and/or guanyl-cyclase. In other tissues (smooth muscle) their biological action is associated with changes in transcellular flows of calcium. Prostaglandins and thromboxane have many biological properties. Their effects are local, as they are produced in small quantities and promptly metabolized. They act more often as cell function modulators than as essential mediators. The often conflicting biological actions of these icosanoids involve: a) smooth muscles (stimulation or relaxation of blood vessel, respiratory tract, digestive tract and genitourinary tract musculatures); b) platelets (induction or inhibition of aggregation); c) the inflammatory reaction; d) the cellular fluid and electrolyte transports; e) and certain metabolic functions (lipolysis, insulin release, renin release, mobilization of bone calcium...). The advances achieved over the last decade now provide some insight into the significance of the physiologic role of icosanoids. Several prostaglandins, as well as some of their analogues, are already being used as therapeutic agents. In the future, rational manipulation of dietary fatty acids and development of selective inhibitors can be expected to provide the necessary tools for better controlling the icosanoid system in medicine.
 ...
PMID:[Prostaglandins and thromboxanes]. 632 4

Rats were adrenalectomized and injected for 7 days with dexamethasone (DEX) or deoxycorticosterone. Kallikrein and prekallikrein were assayed in urine and in a basolateral membrane-enriched fraction. The activities of renin and phospholipase A2 were also determined in the fraction. Adrenalectomy significantly decreased active kallikrein in urine. Administration of deoxycorticosterone raised the level of active kallikrein in urine without affecting the concentration of prekallikrein. Rats treated with DEX only had high Na+ and low active kallikrein excretion. The total kallikrein level (active kallikrein together with prekallikrein), however, returned to normal because DEX elevated the prekallikrein level. DEX also increased the prekallikrein concentration in the membrane-enriched fraction. Renin activity in the membrane-enriched fraction was enhanced by adrenalectomy but suppressed by either corticosteroid. The changes in the concentration of plasma renin were qualitatively similar but quantitatively different. The activity of phospholipase A2 in the membrane-enriched fraction was enhanced only by deoxycorticosterone. Thus, both gluco- and mineralocorticoids increased kallikrein excretion in the adrenalectomized animals, but DEX was apparently effective at a lower dose than deoxycorticosterone. DEX increases the prekallikrein concentration in urine and on the basal membrane of distal tubular cells and, in addition, may prevent its conversion by releasing an inhibitor of a prekallikrein activator.
 ...
PMID:Regulation of rat urinary and renal kallikrein and prekallikrein by corticosteroids. 634 76

Vipera russelli venom contains several isoenzymes of phospholipase A2 (PLA2) which were isolated by column chromatography. The effects of PLA2 fractions on blood pressure, plasma prostacyclin level and renin activity were studied in normotensive and renal hypertensive rats. PLA2 fractions II-5, II-7, III-3 and III-6 (0.1 mg/kg) injected i.v. into rats decreased the arterial blood pressure. The hypotensive action of PLA2 fractions was not affected by heat treatment (70-80 degrees C, 30 min, pH 6.8). After indomethacin (30 mg/kg, i.v.), the hypotensive response to PLA2 was markedly reduced. Plasma prostacyclin (PGI2) and thromboxane A2 (TXA2) levels were measured by radioimmunoassays of their degradation products, 6-keto-PGF1 alpha and TXB2, respectively. PLA2 fractions (0.1 mg/kg) induced an increase in plasma PGI2 and TXA2 levels. There was a positive linear correlation between the PLA2-induced hypotensive effect and the ratio of increased 6-keto-PGF1 alpha to TXB2 (r = 0.83) in normotensive rats. In renal hypertensive rats, the increase in PGI2 level was larger than in normotensive rats. Plasma renin activity was also measured by the radioimmunoassay. Plasma renin activity was reduced by PLA2 fractions in renal hypertensive rats, but not in normotensive rats. These results suggest that the hypotensive effect of PLA2 fractions in normotensive rats may be partly due to the increase in plasma prostacyclin and thromboxane A2 levels. In addition to the larger increase in plasma PGI2 level, the reduction in plasma renin activity may also contribute to the greater hypotensive effect of PLA2 fractions in renal hypertensive rats.
 ...
PMID:Effects of phospholipases A2 from Vipera russelli snake venom on blood pressure, plasma prostacyclin level and renin activity in rats. 637 70

Two different plasma membrane enriched fractions were isolated from the homogenized rat kidney by differential centrifugation in dextran or sucrose. Marker enzymes and morphological studies indicated that one fraction (BLM) was enriched in membrane particles originating from the basolateral membrane of tubular cells, while the other, the PM fraction, contained membrane from the luminal side. Membrane-bound kallikrein and renin were found in both fractions. Kallikrein activity was enhanced by phospholipase A2, melittin and detergents. Renin activity was greatly increased after solubilization by the same agents. In addition to bound kallikrein and renin BLM contained a prekallikrein which was activated by trypsin or plasmin. BLM prekallikrein has a slower electrophoretic mobility and a higher molecular weight than urinary or glandular kallikrein. The basal membrane of tubular cells appears to contain all of the essential enzyme components of the kallikrein and renin systems. Kallikrein of the PM fraction is probably released into the urine, while prekallikrein and kallikrein from basal membrane may be the source of kallikrein in lymph and renal venous effluent. Membrane-bound renin could be a form of renin retained by the kidney.
 ...
PMID:Prekallikrein, kallikrein and renin in membrane fractions of rat kidney. 675 83

The adequate biological function of the renin-angiotensin system in blood pressure regulation and volume control involves additional factors for a fully balanced response. This includes arachidonic acid-derived lipid mediators, the eicosanoids. Angiotensin II (Ang II) causes (AT1)-receptor mediated stimulation of phospholipase C, resulting in generation of IP3 (inositol triphosphate) and activation of protein kinase C, elevated cytosolic Ca+ and stimulation phospholipase A2. These processes culminate in the generation of cell-specific eicosanoids and their autocrine action on the generating cell or paracrine effects on cells in the vicinity. In vascular tissue, liberated arachidonic acid is mainly converted into vasodilator prostaglandins, i.e. prostacyclin (PGI2) and PGE2. These prostaglandins may attenuate any direct Ang II-induced vasoconstriction, lower systemic vascular resistance and stimulate renal sodium excretion. In some vessels, arachidonic acid released by Ang II may also be converted to vasoconstrictor eicosanoids, i.e. thromboxane A2, PGF2 alpha and 12-HETE. The biological significance of endogenous eicosanoid generation becomes evident if vasoactive eicosanoids become limiting factors for maintaining homoiostasis, i.e. in the fetal circulation, Bartter's syndrome and congestive heart failure where vasodilating eicosanoids (PGE2, PGI2) are involved in maintenance of low vascular resistance and reduced or absent vasoconstriction by Ang II. Vasoconstrictor eicosanoids (thromboxane A2, PGF2 alpha, 12-HETE) contribute to high blood pressure in (renovascular) hypertension and pregnancy-induced hypertension. Alternatively, generation of vasodilator prostaglandins may be reduced in these situations. The vascular renin-angiotensin system is subject to the action of a number of drugs and chemicals, most notably specific inhibitors of the angiotensin-converging enzyme and drugs affecting kidney function (furosemide) and/or vessel tone (propranolol).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Prostaglandin-mediated actions of the renin-angiotensin system. 849 70

The angiotensin AT1 receptor mediates renal prostaglandin (PG) E2 production through stimulation of phospholipase A2. Blockade of the AT2 receptor potentiates the angiotensin II-induced increase in PGE2 levels. In the kidney, PGE2 is converted to PGF2 alpha mainly by the enzyme PGE 9-ketoreductase. We hypothesized that the conversion of PGE2 to PGF2 alpha is inhibited by AT2 receptor blockade, resulting in the observed increase in PGE2 levels. Using a microdialysis technique, we monitored changes in renal interstitial fluid PGE2 and PGF2 alpha in response to 5 days of sodium depletion alone or a combination of sodium depletion and intravenous infusion of the AT1 receptor blocker losartan or the AT2 receptor blocker PD-123319 in conscious rats. We utilized the PGF2 alpha-to-PGE2 ratio as an indirect measure of the rate of renal PGF2 alpha formation. Sodium depletion increased PGE2, PGF2 alpha, and the PGF2 alpha-to-PGE2 ratio. During sodium depletion, losartan decreased PGE2 and PGF2 alpha and did not change the PGF2 alpha-to-PGE2 ratio. In contrast, PD-123319 increased PGE2, decreased PGF2 alpha, and decreased the PGF2 alpha-to-PGE2 ratio. These data demonstrate that activation of the renin-angiotensin system during sodium depletion physiologically increases renal conversion of PGE2 to PGF2 alpha. The increase in renal production of PGF2 alpha is mediated through stimulation of the angiotensin AT2 receptor.
 ...
PMID:The subtype 2 angiotensin receptor regulates renal prostaglandin F2 alpha formation in conscious rats. 932 92

1. Angiotensin II (Ang II), the main effector of the renin-angiotensin system, exerts its vasoconstrictory and trophic actions on smooth muscle cells via AT1 receptors. However, Ang II does not act only on smooth muscle cells, as Ang II receptors are also present in endothelial cells. 2. The receptor type on these cells differs depending on the origin of the endothelium and the species. The rat endothelial receptors are mostly of the AT1 type, but AT2 receptors have also been found. The pharmacological characteristics of the AT1 receptors on endothelial cells are similar to those of other cell types. 3. Ang II stimulates phospholipase C and phospholipase A2 activation via the AT1 receptor in endothelial cells. Ang II also stimulates the tyrosine phosphorylation of several proteins in these cells. 4. Some studies suggest that the AT1 receptor mediates the release of vasodilator molecules by endothelial cells and could modulate Ang II effect on smooth muscle cells. Ang II may also inhibit endothelial cell growth via the AT2 receptor. Finally, endothelial Ang II receptors may be implicated in the regulation of fibrinolysis.
 ...
PMID:Angiotensin II receptors in endothelial cells. 934 11

Recently, the binding of renin and prorenin to cellular receptors with the subsequent generation of second messengers and the production of physiological effects has been demonstrated. In addition, the internalization of prorenin by target cells has been associated with increased cellular synthesis of angiotensin and cardiac pathology. Also, a renin transcript lacking the sequences encoding a secretory signal has been reported, and this transcript appears to produce a renin that acts in the cell that synthesized it. Some years ago, we coined the term intracrine for a peptide hormone or factor that acts in the intracellular space either after internalization or retention in its cell of synthesis. Thus defined, a wide variety of peptides display intracrine functionality, including hormones, growth factors, transcription factors, and enzymes. For example, considerable evidence indicates that angiotensin II is an intracrine. Also, general principles of intracrine functionality have been developed. Thus, recent evidence demonstrates that the prorenin/renin molecule is an intracrine enzyme. Here, the actions of intracrine enzymes (angiogenin, phosphoglucose isomerase, phospholipase A2, granzyme A and B, thioredoxin, platelet-derived endothelial growth factor, and serine protease inhibitors) are reviewed. The relation of prorenin/renin to other intracrine enzymes, and to intracrines in general, is discussed.
 ...
PMID:Intracellular renin and the nature of intracrine enzymes. 1286 Aug 32

The juxtaglomerular apparatus in the kidney is important in controlling extracellular fluid volume and renin release. The fluid load to the distal tubule is first sensed at the macula densa site via the entry of NaCl, through a Na, K, 2Cl co-transport mechanism. The next step is unclear, but there is recent evidence of an increased macula densa cell calcium concentration with a reduction in fluid load to the macula densa. An increase in macula densa cell calcium could activate phospholipase A2 to release arachidonic acid, the rate-limiting step in the formation of prostaglandins. Recent evidence suggests that the prostaglandin formed is PGE2, a potent stimulator for renin release. Recent evidence has also shown that adenosine has an important function in the juxtaglomerular apparatus. It stimulates calcium release in afferent arteriolar smooth muscle cells, leading to contraction of the afferent arteriole as part of the tubuloglomerular feedback mechanism, and inhibits renin release. Thus, renin release from the afferent arteriole is mediated partly through formation of PGE2, and partly through the reduction of adenosine formation that inhibits renin production.
 ...
PMID:Mechanisms for macula densa cell release of renin. 1528 60


<< Previous 1 2 3 Next >>