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

1. The protease inhibitors Trasylol and soyabean trypsin inhibitor prevented the activation of plasma inactive renin by acid. 2. N-Ethylmaleimide inhibited acid-activation to some extent but o-phenathroline had no effect. 3. Acid-activation of the inactive renin in human plasma is mediated by a serine protease.
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PMID:An endogenous protease activating plasma inactive renin. 3 3

1. We have found that 'acid'-activation of inactive human plasma renin is a two-phase process. About 30% of activation occurs during dialysis to pH 3.3; the remaining 70% occurs at alkaline pH. 2. The 'alkaline phase' of activation has a pH optimum between 7.5 and 8.4. It is inhibited by unacidified plasma and by soya-bean or lima-bean trypsin inhibitors. 3. 'Cryoactivation' of inactive plasma renin, which occurs at -4 degrees C and alkaline pH, is also inhibited by soya-bean or lima-bean trypsin inhibitors and by the serine protease inhibitors diisopropylphosphorofluoridate and benzamidine. 4. Thus endogenous neutral serine proteases participate in the activation of inactive plasma renin in vitro. Their action is prevented in the circulation by inhibitors which are inactivated by acid or cold.
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PMID:Activation of inactive plasma renin: evidence that both cryoactivation and acid-activation work by liberating a neutral serine protease from endogenous inhibitors. 3 4

Plasma prorenin is an inactive form of renin (EC 3.4.99.19) that can be converted to active renin in acid-treated plasma by an endogenous serine protease that is active at alkaline pH (alkaline phase activation). To identify this enzyme we first tested the ability of Hageman factor fragments, plasma kallikrein (EC 3.4.21.8), and plasmin (EC 3.4.21.7) to activate prorenin in acid-treated plasma. All three enzymes initiated prorenin activation; 50% activation was achieved with Hageman factor fragments at 1 microgram/ml, plasma kallikrein at 2-4 microgram/ml, or plasmin at 5-10 microgram/ml. We then showed that the alkaline phase of acid activation occurred normally in plasminogen-free plasma but was almost completely absent in plasmas deficient in either Hageman factor or prekallikrein; alkaline phase activation was restored to these latter plasmas when equal parts were mixed together. Therefore, both Hageman factor and prekallikrein were required for alkaline phase activation to occur. We then found that, although plasma kallikrein could activate prorenin in plasma deficient in either Hageman factor or prekallikrein, Hageman factor fragments were unable to activate prorenin in prekallikrein-deficient plasma. These studies demonstrate that alkaline phase prorenin activation is initiated by Hageman factor-dependent conversion of prekallikrein to kallikrein which, in turn, leads to activation of prorenin. In this fashion, we have revealed a possible link between the coagulation-kinin pathway and the renin-angiotensin system.
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PMID:Initiation of plasma prorenin activation by Hageman factor-dependent conversion of plasma prekallikrein to kallikrein. 4 5

In this paper, we present the amino-terminal sequence of rat tonin, an endopeptidase responsible for the conversion of angiotensinogen, the tetradecapeptide renin substrate, or angiotensin I to angiotensin II. It is shown that isoleucine and proline occupy the amino- and carboxy-terminal residues respectively. The N-terminal sequence analysis permitted the identification of 34 out of the first 40 residues of the single polypeptide chain composed of 272 amino acids. These results showed an extensive homology with the sequence of many serine proteases of the trypsin-chymotrypsin family. This information, coupled with the slow inhibition of tonin by diisopropylfluorophosphate, classified this enzyme as a selective endopeptidase of the active serine protease family.
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PMID:N-Terminal amino acid sequence of rat tonin: homology with serine proteases. 21 93

We previously demonstrated high levels of inactive renin (IR) in nephrectomized rat plasma which provided evidence for extra-renal sources of IR. However, the sources of IR were unknown. This study examined whether the adrenal gland is capable of producing active renin (AR) and IR, using explants of adrenal capsules (glomerulosa portions) from control and nephrectomized (Nepex) rats. Explants from both control and Nepex rats produced large quantities of IR and small quantities of AR. The productions of both IR and AR in Nepex rats were significantly greater than in control rats. High potassium culture medium markedly increased IR and slightly, but significantly, enhanced AR in both control and Nepex rats. On the other hand, sodium had little effect on either IR or AR. A renin-angiotensin system has been reported in the adrenal gland. Recently, a prorenin activating enzyme was demonstrated in the kidney and the aortic wall. The next study was performed to demonstrate the existence of a prorenin activating enzyme in the adrenal gland, using inactive renin from culture medium from Nepex rat explants as the substrate. A 26 KD component in adrenal zona glomerulosa tissues isolated by Sephacryl S-200 column chromatography, converted IR to AR in IR rich medium. The pH optimum for prorenin activation by the enzyme was 6.5. Inhibitor studies indicate that this enzyme is a serine protease. These data suggest that (1) the adrenal gland is an extra-renal source of inactive renin and (2) a prorenin activating enzyme exists in the adrenal gland.
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PMID:Production of active and inactive renin by adrenal explant cultures and the existence of a prorenin activating enzyme in the adrenal gland. 145 51

The renin-angiotensin system originally was thought to be responsible for only renovascular hypertension, but the development and use of various inhibitors of this system have produced much evidence for its participation in many forms of hypertensive disease. Tissue renin-angiotensin system also may play a major role in blood pressure control. Chronic clinical as well as animal use of converting enzyme inhibitors results in levels of angiotensin II that are equivalent to those found in the normotensive state and higher than those found in the very acute phase of treatment. The source of this conversion possibly may be due to enzymes unrelated to angiotensin converting enzyme. One such enzyme is a very highly specific serine protease isolated from human cardiac tissue. This enzyme exists in human ventricular tissue at levels four to five times that of angiotensin converting enzyme. During chronic treatment of patients with heart failure, angiotensin I levels become high, and heart tissue levels of angiotensin II may become elevated because of the conversion to angiotensin II by this serine protease. This conversion in turn may possibly increase inotropy of the heart, whereas the peripheral resistance remains low because of the reduction of angiotensin II in the circulation.
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PMID:Angiotensin I and II. Some early observations made at the Cleveland Clinic Foundation and recent discoveries relative to angiotensin II formation in human heart. 193 74

To clarify the possible conversion of prorenin in renin granules where conversion reportedly occurred, we investigated whether the renin granule fraction of the kidney could activate prorenin to the active form. Renin granules were isolated from the dog kidney cortex by discontinuous sucrose density gradient centrifugation. Human active renin was quantified by immunoradiometric assay which could detect only the human active renin but not the inactive human renin or dog renin. Inactive renin from human amniotic fluid was incubated with the subcellular fraction of the dog kidney cortex. The renin granule fraction that showed the highest renin activity stimulated the inactive renin to become the active form. The membrane preparation obtained from the renin granule fraction by freezing and thawing the fraction in low osmolarity retained the activity of renin activation. Other subcellular fractions showed less renin activation. The optimal pH for renin activation by the membrane was pH 5.0 to 6.0. The activation depended on the time of incubation and concentration. The activation was inhibited by N-ethylmaleimide but not by EDTA or serine protease inhibitors. These results suggest that renin is processed by a membrane bound protease in renin granules.
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PMID:Human renin activation by protease from the renin granule fraction of the dog kidney cortex. 198 85

Renin is produced from an inactive precursor, prorenin, through proteolytic cleavage at paired basic amino acid residues. In this study, an enzyme which specifically cleaves mouse Ren 2 prorenin at the paired basic residues has been purified from mouse submandibular gland by CM-Toyopearl chromatography, antipain-Sepharose chromatography, and isoelectric focusing. This enzyme, named prorenin converting enzyme, consists of two polypeptide chains of 17 and 10 kDa. The enzyme has an isoelectric point of 9.5-9.8, and its pH optimum is between 7.5 and 8.5. It specifically cleaves the peptide bond on the carboxyl side of the Arg at the Lys-Arg pair of mouse Ren 2 prorenin to yield mature renin but does not cleave mouse Ren 1 and human prorenins. Studies on the effects of inhibitors indicate that this enzyme is a serine protease that differs from the enzymes processing other prohormones at paired basic amino acid residues.
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PMID:A processing enzyme for prorenin in mouse submandibular gland. Purification and characterization. 218 Sep 37

1. Changes in tension in response to cumulative additions of angiotensins (i.e., angiotensinogen, angiotensin I and angiotensin II), bradykinin and acetylcholine were monitored isometrically on ring preparations from porcine interlobar renal arteries. 2. Angiotensins consistently elicited contractile responses, whereas both bradykinin and acetylcholine produced relaxation of the arterial rings when active tone was induced by prostaglandin F2 alpha. 3. Contractile responses to angiotensin II could be completely blocked by the combined action of the cyclo-oxygenase inhibitor, indomethacin (1 microM) and the lipoxygenase inhibitor, nordihydroguairetic acid (NDGA, 10 microM). 4. Relaxant responses to bradykinin were unchanged during blockade of thromboxane A2 synthesis by dazoxiben (30 microM) and proved to be largely resistant to blockade by indomethacin (1 microM) and the prostaglandin I2 (prostacyclin) synthesis inhibitor, tranylcypromine (40 microM). 5. The angiotensin receptor blocker, saralasin (10 and 100 nM) antagonized responses to angiotensinogen, angiotensin I and angiotensin II effectively and with similar potency. Enalaprilic acid, the active metabolite of the converting enzyme inhibitor enalapril (300 nM), attenuated responses to angiotensin I but failed to inhibit those to angiotensinogen up to 1 microM. The serine protease kallikrein (0.001 to 1 mu ml-1) produced a dose-dependent shift to the left of the concentration-response curve for angiotensinogen. 6. It is suggested that the porcine interlobar renal artery possesses a local renin-angiotensin system with activatable angiotensin II forming enzyme(s) within the vessel wall.
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PMID:Pharmacological evidence for the existence of a local renin-angiotensin system in porcine interlobar renal arteries. 228 72

Using pure recombinant human prorenin as a substrate, we have identified an enzyme in human kidney that accurately processes prorenin to active renin (EC 3.4.23.15). In the crude homogenate, the predominant activity of this potential renin-processing enzyme (RPE) converted the Mr 47,000 inactive prorenin to Mr 44,000 active renin and had a pH optimum of approximately 6. The activity was blocked by cysteine protease inhibitors, but not by pepstatin, EDTA, or serine protease inhibitors. This RPE activity was not detected in a similarly prepared homogenate of human chorion decidua tissue, which produces primarily prorenin, or in human plasma. The activity was purified 100-fold by ammonium sulfate precipitation, p-chloromercuribenzoate affinity chromatography, and chromatofocusing. The partially purified enzyme has a Mr of approximately 27,000 and an isoelectric point in the pH 4.8-5.6 range. The activity in the purified RPE preparation had the same pH optimum as that in crude homogenate, cleaved the prosegment at the same site used by the kidney in vivo based on amino-terminal sequencing of the processed renin, and did not degrade prorenin or renin. These data suggest that the cysteine protease we have isolated is a candidate for authentic renal RPE.
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PMID:Identification of an enzyme in human kidney that correctly processes prorenin. 240 45


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