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)

Urinary kallikrein has been reported to activate human plasma inactive renin. Our previous report suggests that rat urinary kallikrein releases active renin from rat renal cortical slices. Recently, McPartland et al. were able to separate the A esterase activity of male rat urine into two components: A1 and A2. To evaluate whether these other urine arginine esterases release renin from the kidney, esterases A1 and A2 were isolated from male rat urine using DEAE-Sephadex chromatography and superfused to rat renal cortical slices. The renin-stimulating action of these enzymes was compared to that of rat urinary kallikrein. Rat urinary kallikrein stimulated renin release in a dose-dependent fashion between 70--140 milliesterase units (mEU)/ml. Esterase A2 dose stimulated renin release significantly between 120--140 mEU/ml. However, esterase A1 did not stimulate renin release at concentrations between 70--140 mEU/ml. Although Trasylol completely abolished kallikrein and esterase A2 stimulated renin release, soybean trypsin inhibitor blocked only esterase A2-stimulated renin release. The physiological role and site of origin of the A1 and A2 esterases is unknown. However, similar to kallikrein, esterase A2 is a potent stimulator of renin release and may be physiologically important for the release and activation of renin in the kidney.
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PMID:Effects of rat urinary arginine esterases on rat kidney to release renin. 616 23

Renal kallikrein was reported to activate human inactive renin and to release active renin from rat renal cortical slices. To evaluate the role of renal kallikrein in the control of renin release in vivo, Trasylol and soybean trypsin inhibitor (SBTI) were used to determine whether they can inhibit renin release stimulated by the administration of furosemide and a 2-wk low-sodium diet. Plasma renin activity (PRA) was increased by furosemide and also by the low-sodium diet. Urinary kallikrein excretion was increased by the sodium depletions. Trasylol did not affect basal PRA; however, it inhibited PRA and urinary kallikrein excretion, when stimulated by furosemide and by a low-sodium diet. These results suggest that furosemide and low-sodium diet act on the kidney to release renin via protease production. Because SBTI affected neither PRA nor urinary kallikrein excretion stimulated by these sodium depletions, it is suggested that renal kallikrein may play an important role in the control of renin release stimulated by furosemide and by low-sodium diet.
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PMID:Role of renal kallikrein in control of renin release in conscious rats. 618 20

Inactive renin in normal plasma, Factor XII-deficient plasma and prekallikrein-deficient plasma was fully activated by dialysis to pH 3.0 for 24 hours at 4 degrees C. This activation was reversed after neutralization and incubation of the plasma at 37 degrees C. The reversible activation-inactivation was not affected by the presence of soya bean trypsin inhibitor. If acidified normal plasma was neutralized and stood at 4 degrees C, plasma kallikrein, but not plasmin, was generated. This rendered the initial acid-activation irreversible. Since no kallikrein was generated in the deficient plasmas, the acid-activation was reversible in these plasmas even after neutralization and standing at 4 degrees C. Thus the apparent activation of inactive renin by kallikrein in acidified, neutralized plasma is not a direct action by the serine protease on inactive renin but a two-stage process in which the inactive renin is first fully activated by acid treatment and the reverse reaction is prevented by plasma kallikrein.
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PMID:The reversible activation of inactive renin in human plasma: role of acid and of plasma kallikrein and plasmin. 621 88

Tonin is an enzyme found in the rat submaxillary glands which liberates angiotensin II from angiotensinogen, the Skeggs tetradecapeptide renin substrate, and angiotensin I. Tonin hydrolyzes benzoyl-arginine ethyl ester, benzoyl-arginine methyl ester, tosyl-arginine methyl ester, benzoyl-arginine p-nitroanilide and other small synthetic substrates at an optimum ph of 9.0. Tonin shows, however, a great specificity with respect to angiotensin I. Tonin is inhibited by diisopropyl fluorophosphate and phenylmethylsulfonyl fluoride at high concentrations (greater than 10(-2) M) and by soybean trypsin inhibitor and aprotinin. Tonin is thus an esteroprotease of the class of the serine protease with trypsin- and chymotrypsin-like activity. Tonin belongs to the same family of enzyme as glandular kallikrein and the gamma subunit of the nerve growth factor.
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PMID:Tonin, an esteroprotease from rat submaxillary glands. 626 71

We have studied the dog as a potential model for the human plasma prorenin-renin system. On a regular sodium intake, healthy conscious dogs apparently have a much lower plasma renin activity (PRA) than healthy human volunteers. Cryoactivation of prorenin is virtually absent in dogs, in contrast to that in humans, but becomes more effective after preacidification of the plasma. The concentration of trypsin required for optimal activation of prorenin is 6 to 10 times higher for dog plasma, revealing a prorenin:renin ratio about 10 times greater than in humans. Dialysis of posttryptic plasma decreases the PRA, but it remains 5 times higher than in pretryptic plasma, indicating that activation is not totally dependent on any renin system component that has been rendered dialyzable by trypsin, e.g., substrate converted to tetradecapeptide (TDP). This argues against the view that tryptic activation is attributable to angiotensin production from TDP by the action of cathepsin D, rather than from new renin converted from prorenin. The posttryptic increase in PRA is evident whether plasma incubation is carried out at pH 6.0 or at 7.4, and can be largely blocked by pepstatin, which also implicates a prorenin-renin mechanism rather than TDP-cathepsin. The low PRA in dogs, the negligible cryoactivation and its improvement by preacidification, and the requirement and tolerance of high trypsin concentrations, all point to greater protease inhibition in dog plasma and/or departures from the enzyme(s) responsible for human prorenin activation. Moreover, the tryptic activation of prorenin is not completed quickly as in human plasma, but carries over into the posttryptic stage of angiotensin generation, even in the presence of excess soybean trypsin inhibitor (SBTI), and other potent inhibitors. Such ongoing prorenin activation cannot be attributed only to trypsin itself, nor to kallikrein (both are inhibited by SBTI), but rather to some other enzyme(s) derived by the action of trypsin. This new prorenin convertase activity (possibly renin itself) can be effectively transferred from trypsinized to control dog plasma, in which it greatly accelerates prorenin activation. Thus, contrary to other reports, dog plasma has a high content of activatable prorenin, and with appropriate methodological changes, the dog can be used as an animal model for physiological and biochemical studies of the prorenin-renin system.
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PMID:Plasma prorenin in humans and dogs. Species differences and further evidence of a systemic activation cascade. 634 Dec 16

The present study was undertaken to quantify the circulating kinins in patients with various cardiovascular diseases using a newly developed radioimmunoassay technique and to evaluate this method in terms of its clinical application. For the determination of bradykinin (BK), this assay uses a rabbit anti-serum which has been injected with kallidin. This assay shows good specific activity, recovery and reproducibility. In order to avoid the formation of kinin as well as to block its inactivation, human blood samples were collected with a polypropylene syringe containing an inhibitor mixture (EDTA, trasylol, 1-10-phenanthroline, soybean trypsin inhibitor, polybrene). 1) The plasma BK concentration in normal human subjects, in patients with essential hypertension, effort angina and other cardiac diseases were 12.2, 9.2, 8.0 and 14.0 pg/ml, respectively. 2) Thirty min after captopril (12.5 mg, p.o.) administration, blood pressure and pulmonary wedge pressures decreased, and cardiac output increased accompanied with increases in plasma renin activity, plasma BK concentration and plasma norepinephrine concentration. 3) During the cold pressor test, both plasma BK concentration and blood pressure increased in the normal human subjects, whereas plasma BK levels decreased and blood pressure increased in the patients with hypertension. This radioimmunoassay for plasma BK determination makes it possible to measure plasma BK concentration in patients with various cardiac diseases.
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PMID:[Plasma bradykinin concentration in patients with cardiovascular diseases]. 636 31

In human plasma, trypsin activates "prorenin" within 1 min at 23 degrees C. It is quickly neutralized by endogenous inhibitors, and the subsequent hourly expression of old and new renin activity (PRA) is relatively consistent during 15, 30, or 60 min incubation at 37 degrees. In dog plasma, prorenin activation requires much higher trypsin concentrations - 3-5 mg/ml, vs 0.5-1.5 mg in humans - implying a higher content of endogenous protease inhibitors, and/or the lack of some endogenous mediator of the action of trypsin. These could also be partly responsible for the observed lack of cryoactivation in dogs. The effect of trypsin in dog plasma does not end abruptly as in humans. A post-tryptic prorenin "convertase" continues to act at 37 degrees, steadily increasing the hourly rate of angiotensin generation as the incubation is prolonged. Neither lima bean trypsin inhibitor (LBTI) nor endogenous inhibitors fully inhibit this trypsin-induced convertase. It is transferable to normal plasma, where it raises the PRA. Pepstatin severely inhibits this effect, most probably by inhibiting the new renin, possibly also by inhibiting the convertase itself. Rat plasma appears intermediate between human and dog plasmas in some respects. Trypsin activates prorenin well at 4 mg/ml, when exposed for 30 min at 23 degrees, provided the subsequent PRA incubation stage is kept short, e.g. 10 vs 30 min. This implies a low tolerance to effective concentrations of trypsin, presumably attributable to the nature and/or quantity of endogenous protease inhibitors. The amount of prorenin, as judged by activation, equals that of dogs. However, active renin is distinctly higher in rats, possibly due to the stressful influence of anesthesia and blood collection. This greatly reduces the prorenin: renin ratio in rats relative to dogs, and brings them closer to the human ratio. Clamping off the renal blood vessels while blood is collected, lowers the basal PRA, and raises the prorenin:renin ratio. Thus, prorenin is detectable in all 3 species, but the best methods for activating it are quite different, implying marked differences in the mechanisms involved.
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PMID:Peculiarities of plasma "prorenin" measurements in man, dog, and rat, and their theoretical implications. 675 92

Puff adder venom, which has been pretreated with phenylmethylsulphonyl fluoride and extensively dialysed, is capable of destroying selectively proteinase inhibitory activity in human plasma by an action of an EDTA-sensitive venom proteinase. We found that incubation of 1/5 vol. of such venom with human plasma at 25 degrees C leads to a concomitant increase in renin to 4.4 times control by 5 h. The activation of inactive renin was abolished by 10 mM EDTA and the rate of activation was reduced by 50% in the presence of 5 mM phenylmethylsulphonyl fluoride and by 90% when 0.32 mg/ml soybean trypsin inhibitor and 5 mM N-ethylmaleimide were added as well. The venom proteinase thus appears to activate inactive renin via an activation of endogenous plasma proteinases. This may be accomplished either by activation of proteinase precursors or action on proteinase inhibitor-proteinase complexes. By destroying proteinase inhibitors at the same time as it activates endogenous proteinases, Bitis arietans metalloproteinase would appear to be particularly useful for studies of the activation of inactive renin in human plasma, since endogenous proteinases are then free to activate inactive renin without subsequent inhibition by endogenous proteinase inhibitors.
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PMID:Activation of inactive renin during the selective destruction of proteinase inhibitors in human plasma by a metalloproteinase in Bitis arietans venom. 698 10

Kallikrein is present in the renal tubule near the macula densa, and it has recently been shown to activate inactive renin in human plasma. We recently showed that kallikrein was a potent stimulus of renin release and increased renin secretion in a dose-dependent fashion. To study its effect on renal renin release, we superfused rat renal cortical slices with purified rat urinary kallikrein. Kallikrein-stimulated renin release was completely abolished by trasylol and by amiloride, but was not affected by soybean trypsin inhibitor. Indomethacin did not block kallikrein action, indicating that kallikrein's effect is not mediated via kinin generation and prostaglandins. Kallikrein-stimulated renin release was not blocked by propranolol, trasylol did not block isoproterenol, and dibutyryl cyclic AMP stimulated renin release, indicating that kallikrein may not play a role in the beta-adrenergic mechanism of renin release. There was no demonstrable acid-activatable or kallikrein activatable renin in the superfusate, suggesting that all of the renin release was in the active form. Cathepsin D and plasmin also stimulated renin release from kidney slices in pH 6.0 buffer, whereas trypsin and pepsin did not. Our results support the hypothesis that kallikrein may play a role in the secretion of renin by the kidney. Other proteases can also release renin from the kidney.
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PMID:Direct action of kallikrein and other proteases on the renin-angiotensin system. 702 11

Semipurified soybean trypsin inhibitor added to rat and human plasma leads to a concentration dependent decrease in the rate of angiotensin I generation. This inhibition is due to binding of renin substrate to the inhibitor. Renin substrate present in nephrectomized rat plasma was more susceptible to binding than substrate of the normal rat suggesting structural differences in the substrate generated following nephrectomy. Because trypsin inhibition is necessary for measurement of active and inactive renin, we examined several alternate trypsin inhibitors. The Bowman-Birk inhibitor from soybean had similar actions as purified soybean trypsin inhibitor while trypsin inhibitors from lima bean and chicken did not depress renin substrate, but did have variable effects on the measured levels of active and total plasma renin. Surprisingly, crude soybean trypsin inhibitor did not suppress renin substrate and actually increased angiotensin I generation during PRA and PRC measurements. Since the crude preparation did not suppress renin substrate, changes in the specificity of the inhibitor may occur during its purification. The augmentation of PRA and PRC may be related to angiotensinase inhibitory actions.
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PMID:Inactivation of renin substrate by soybean trypsin inhibitors: implications for measurement of circulating inactive renin. 840 14


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