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)

The influence of pH and angiotensinase inhibitors on the in vitro generation of angiotensin I during PRA measurements has been investigated. PRA values obtained at pH 5.7 are higher than those obtained at pH 7.4. At pH 5.7, values obtained using diisopropylfluorophosphate (DRP 9 mM) as an angiotensinase inhibitor are higher than values obtained with a mixture of dimercaprol (BAL, 1.6 mM) and hydroxyquinoline (8-OHQ, 3 to 4 mM). Since the two methods for inhibiting angiotensinase are completely and equally efficient, it is suggested that these inhibitors might interfere with the renin angiotensinogen reaction. Significant correlations are observed between the PRA values obtained by the different methods which have been studied. Using an incubation pH of 5.7, and BAL and 8-OH quinoline as angiotensinase inhibitors, the distribution of PRA values in a population of 124 hospitalized hypertensive patients ingesting a normal sodium diet had been studied, and it has been demonstrated that the sensitivity of this method of measurement can detect small changes in PRA in patients with low renin activity.
 ...
PMID:Methodologic problems in plasma renin activity measurements. 1 Jul 27

To examine extrarenal sources of "renin-like" activity plasma was obtained from 19 anephric males. Plasma renin activity (PRA), concentration (PRC) (obtained after addition of exogenous renin substrate) and total renin concentration (TRC) (obtained after acid-activation of plasma and subsequent incubation with exogenous renin substrate) demonstrated values for several anephric patients comparable or above those seen in plasma from 10 normal subjects. Incubation of untreated plasma (PRA and PRC) and acid-dialyzed plasma (TRC) for angiotensin I generation was performed at pH 7.5, at 37 degrees C with EDTA, dimercaprol, and 8-OH-quinoline as angiotensinase and converting enzyme inhibitors. The pH optimum for acid-activation of TRC in anephric plasma was the same as that in normal plasma (pH 3.3). Molecular weight determinations following Sephadex gel chromatography demonstrated that the renin-like enzyme in normal plasma had a molecular weight of about 42,000 before and after acid-activation, while that in anephric plasma had a molecular weight of approximately 61,000. A saliva sample from one anephric subject with the highest levels of PRA, PRC, and TRC in plasma also demonstrated measurable amounts of PRA, PRC, and TRC. The molecular weight of this salivary "renin-like" activity also was 61,000. These observations suggest a possible extrarenal source of "renin-like" activity in anephric man. The physiological significance of these studies remains to be clarified.
 ...
PMID:An extrarenal source of "renin-like" activity in anephric man. 1 33

The distribution and biochemical properties of the renin activity present in the dog brain were compared with those of the lysosomal enzyme cathepsin D. Renin and cathepsin activity were present in all brain regions studied, in association with high angiotensinase activity. Brain renin activity was partially purified by ammonium sulfate fractionation and Sephadex gel filtration, resulting in the removal of angiotensinase activity. The specific brain renin activity increased approximately one hundred times during this procedure; cathepsin D activity accompanied the brain renin activity throughout the purification and showed a similar increase in specific activity. The renin and cathepsin activity in the partially purified preparation behaved identically during isoelectric focusing. The partially purified renin and cathepsin activity exhibited saturation kinetics with their respective substrates and were without activity above pH 6.0. Both enzyme activities were irreversibly inhibited by the pepsin inhibitor pepstatin, in nanomolar concentrations. These data, in conjunction with the literature concerning brain cathepsin, suggest that the renin activity in brain is due to cathepsin D, and that this renin activity exhibited by cathepsin D may be of limited significance under physiological conditions.
 ...
PMID:Renin activity in dog brain: enzymological similarity to cathepsin D. 18 Dec 41

The reported presence of large quantities of a high molecular weight form of angiotensin I and II in renin granules from rat kidney cortex was investigated. Subcellular fractionation by differential centrifugation and isopycnic gradient centrifugation confirmed the presence of 'angiotensin I immunoreactive material,' but the distribution resembled that of lysosomes rather than renin granules, mitochondria or protein. The material did not possess pressor properties, was stable to incubation at 37 C and was precipitated by ethanol. Incubation of subcellular fractions with peptidase inhibitors known to inhibit the activity of renal angiotensinases (EDTA, diisopropyl phosphorofluoridate and 2,3-dimercaptopropanol) decreased the level of 'angiotensin I immunoreactive material' in kidney fractions treated by radioimmunoassay. By paper chromatography it was apparent that subcellular fractions were capable of degrading 125I-labelled angiotensin I used as tracer in the radioimmunoassay. The degree of degradation followed the distribution of lysosomes among the fractions and was decreased by the angiotensinase inhibitors. The apparent molecular weight of the major portion of angiotensinase activity persisting despite the presence of angiotensinase inhibitors was 75,000, a value similar to that of 'angiotensin immunoreactive material'inkidney fractions treated with non-ionic detergent. On the basis of the present findings it is suggested that 'angiotensin immunoreactive material' may be largely artifactual, beingcreated by the hydrolysis of tracer by angiotensinase enzymes during radioimmunoassay to form fragments that are no longer capable of binding to the specific antibody. This would produced results that would appear the same as those produced had genuine angiotensin immunoreactivity indeed been present in the samples. Such an effect could, in principle, occur in any competitive protein binding assay and should be tested.
 ...
PMID:Identification of "angiotensin immunoreactive material" in rat kidney. 19 Dec 45

The regional distribution of angiotensinogen, the prohormone of angiotensin I, was examined in rat brain. Quantification of brain angiotensinogen concentration was difficult because of the presence of an endogenous angiotensin I degrading (i.e. angiotensinase) activity which was active at the pH of the renin-angiotensinogen incubation. This degrading activity was unequally distributed throughout the brain, and its presence in homogenates invalidated measured levels of angiotensinogen. Only following removal of the angiotensinase activity by ammonium sulfate precipitation of the prohormone could the distribution of the prohormone be determined. Angiotensinogen was widely distributed throughout 31 brain regions; however there was an approximate 12-fold variation in concentration. Highest levels of the prohormone were found in the dorsal and ventral periventricular hypothalamus, area postrema, organum vasculosum lamina terminalis, periventricular thalamus, dorsal raphe and lateral reticular formation. Significantly lower amounts were found in the parietal cortex, cerebellum, septum and pituitaries. While the majority of regions examined exhibited similar concentrations of angiotensinogen, the demonstration of regions containing either significnatly low or high amounts of prohormone is consistent with a topographical distribution of angiotensinogen in rat brain.
 ...
PMID:Regional distribution of angiotensinogen in rat brain. 21 73

Components of the renin-angiotensin system were studied in established cell culture lines of 3T3 and SV3T3 mouse fibroblasts. The renin content in 3T3 cells was significantly higher than in virus-transformed SV3T3 cells. With time after infection, renin decreased in Simian virus 40 transformed cells, while it increased steadily in mock-infected 3T3 cells. In contrast to renin, angiotensinase activity was higher in SV3T3 cells. Angiotensin II stimulated cell proliferation in 3T3 mouse fibroblasts and decreased their renin content in a dose-related manner. In contrast, saralasin, an angiotensin receptor antagonist, inhibited cell growth in 3T3 and SV3T3 cells and caused an increase of cellular renin concentration. The angiotensin fragments angiotensin (2-8) heptapeptide and angiotensin (4-8) pentapeptide had no effect on cell growth. A significant negative correlation was found between cell proliferation and renin levels in 3T3 and SV3T3 cells irrespective of the treatment. Our results indicate (1) that angiotensin II may be involved in cell growth regulation, (2) that a negative feedback exist between angiotensin II added and intracellular renin content, and (3) that virus infection causes a decrease in intracellular renin synthesis, while non-specific angiotensinase activity is increased under this condition.
 ...
PMID:Effects of angiotensin II and angiotensin II antagonist saralasin on cell growth and renin in 3T3 and SV3T3 cells. 22 Feb 72

Plasma and serum of healthy subjects apparently contain a precursor form of renin, or 'prorenin,' which can be activated by the ice-cold temperature at which samples are customarily handled for prolonged periods in laboratories and blood banks. The effect of such prior cryoactivation for 9 days at 4 degrees C is to increase subsequent plasma renin activity (PRA) at 37 degrees C by 108 +/- 16.3% (mean +/- SE) over the nonactivated control value (P less than 0.001). At a lower temperature (-4 degrees C), the cryoactivation effect is considerably greater than at 4 degrees C. Cryoactivation is not obliterated by the prefreezing of plasma, or reduced by inclusion of bacteriostats. Nor is it attributable to any detectable reduction in angiotensinase activity. In rats, cryoactivation at 4 degrees C is much lower than in humans, suggesting a marked species difference either in prorenin concentration or in the rapidity of its spontaneous conversion after blood collection. Trypsin at near optimal concentrations also consistently activates human plasma prorenin, whether at 4, 23, or 37 degrees C indicating that cold is not an essential concomitant of tryptic activation. In excess, the magnitude of which varies among individuals, trypsin at first produces activation and later a decline in PRA, probably due to degradation of the reactants (prorenin, renin, angiotensinogen) and of the initial product (angiotensin I). The identity of angiotensin I in activated and control plasmas can be established by specific radioimmunoassay, and bioassay. Our data indicate that tryptic activation involves little direct production of angiotensin I but rather converts prorenin, thereby enhancing the angiotensin generating capacity of the plasma renin system itself. Tryptic activation in plasma of anaesthetized dogs is lower than in humans, but higher than in conscious or anaesthetized rabbits in whom the effect appears to be slight. In anaesthetized rats there is virtually no tryptic activation, which is in line with the results by cryoactivation. Since the renin--angiotensin systems of dogs, rabbits, and rats have been extensively studied in experimental models of human hypertension, these observed departures from human levels of cryoactivation and tryptic activation of prorenin deserve further investigation.
 ...
PMID:Cryoactivation and tryptic activation of blood 'prorenin' in normal man and animals. 70 20

One to four weeks after the left renal artery was clipped and the contralateral kidney was left untouched in Sprague-Dawley rats (two-kidney Goldblatt preparation), the clips were removed under ether anesthesia and 10 ml/kg body wt of either 150 mM NaCl (control) or 50% glycerol in water (experimental) were injected intramuscularly. The next day the rats were anesthetized (sodium pentobarbital) and the renal function of both kidneys was measured, after which the renal cortical renin content was measured by incubation of tissue homogenate with angiotensinase-free rat renin substrate. Radioimmunoassay was used to determine the rate of angiotensin I production. Compared with controls, both kidneys of glycerol-injected rats had reduced GFR (left 28, right 18% of controls), increased percentage of fractional water excretion (left 5, right 6 times controls), and increased percentage of fractional Na excretion (left 3, right 4 times controls). Despite large differences in renal renin (left 28, 676, right 1,329 ng angiotensin I/h per mg protein), the extent of renal failure produced by glycerol was equal in the left and right kidneys. These results are inconsistent with the hypothesis that renal renin content is directly related to the severity of glycerol-induced renal failure in rats.
 ...
PMID:Glycerol-induced acute renal failure in the two kidney Goldblatt rat. 91 Sep 21

A two-step purification method is described for the preparation of renin substrate from human plasma. Pooled plasma from women on oral contraceptives is used for the purification. The overall yield of renin substrate is 57%, with a twenty-fold purification. The specific renin substrate content of the preparation, as determined by enzymatic degradation with an excess of human renin, is 2 mug angiotensin I per mg protein. The product has a very low endogenous renin activity and is free from angiotensinase activity. An additional purification step involving affinity chromatography is described. In pilot studies a renin substrate yield of 37% has been achieved, with a hundred-fold purification. The final product has a specific renin substrate content of 10 mug angiotensin I per mg protein. The preparation contains up to 12 different plasma proteins, nine of which have been identified and quantitated.
 ...
PMID:Partial purification of human renin substrate. 93 46

The angiotensinase inhibitor 2,3-dimercaptopropanol (BAL) interferes with peptide-antibody binding when certain sensitive antisera are used in angiotensin I radioimmunoassay systems. Three of nine antisera tested showed sufficient interference to produce serious errors in data obtained using these antisera together with BAL. For PRA determinations in human plasma, at both pH 5.7 and pH 7.3, relationships between different PRA'S are altered, and results of renin stimulation tests are changed in unpredictable ways. Determination of renin concentration in rat plasma does not require use of BAL as inhibitor, and it is best avoided. For human plasma renin determinations, use of BAL-sensitive antisera should be avoided, since there is no satisfactory way to correct data for the resulting error. BAL itself, rather than its oxidation products, is probably the interfering substance. The interference appears to be due to an interaction between BAL and the BAL-sensitive antiserum. It is not related to the known actions of BAL as chelating or reducing agent.
 ...
PMID:Interference by 2, 3-dimercapto-1-propanol (BAL) in angiotensin I radioimmunoassay. 95 83


1 2 3 4 5 6 Next >>