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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)

We studied the effect of aprotinin, a reversible inhibitor of kallikrein and other serine proteases, upon urinary kallikrein and kinin excretion, renal function and hemodynamics, blood pressure, and plasma renin activity (PRA). When aprotinin was administered to anesthetized rats at 10,000 KIU/kg as a bolus, and at 1000 KIU/kg/min infusion for 60 minutes, urinary kininogenase activity and immunoreactive kallikrein, kinins, sodium, potassium, and water excretion, and PRA decreased significantly. Aprotinin also caused a 36% decrease (p less than 0.001) in renal blood flow (RBF), and a 37% decrease (p less than 0.001) in glomerular filtration rate (GFR), although neither blood pressure nor cardiac output changed. The effect of aprotinin on PRA was further studied in conscious rats before and after stimulation of renin release by isoproterenol or furosemide. Aprotinin (5,000 KIU/kg bolus and 1000 KIU/kg/min infusion for 60 minutes) did not alter basal or isoproterenol-stimulated PRA, but it blunted the increase in PRA as stimulated by furosemide. Aprotinin at a higher dose (20,000 KIU/kg bolus and 5000 KIU/kg/min infusion for 60 minutes) significantly lowered blood pressure and increased hematocrit and PRA. These effects may be due to inhibition of serine protease(s) or to other as yet unrecognized properties of this peptide resulting from its highly cationic nature. In conclusion, aprotinin at a low dose decreased kallikrein, kinin, sodium, and water excretion. These decreases may be due to the inhibition of kallikrein and/or other serine proteases or may be secondary to the renal hemodynamic changes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of aprotinin (a serine protease inhibitor) on renal function and renin release. 619 74

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

The renin substrate (angiotensinogen) has been purified from outdated human blood bank plasma. A 100-fold purification was achieved by ammonium sulphate protein fractionation and four successive chromatographic procedures. We show that tonin, a serine protease enzyme found in submaxillary glands of the rat, cleaves the human plasma angiotensinogen, devoid of tonin inhibiting factor(s), at a pH optimum of 5--5.5. It generates a pressor substance that was identified as angiotensin (A) II. The rate of cleavage of the human angiotensinogen preparation by 1 nmol of renin or tonin was calculated to be 1320 nmol AI/h for renin and 26 nmol AII/h for tonin.
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PMID:Formation of angiotensin II by tonin from partially purified human angiotensinogen. 626 47

Tonin is an enzyme of the serine protease family present in different rat tissues which releases angiotensin II (AII) directly from angiotensinogen and the tetradecapeptide renin substrate and from angiotensin I (AI). Tonin potentiates the effect of norepinephrine (NE) in the rat mesenteric artery preparation and in the aortic strips from normal and hypertensive rats. In rabbit aortic and mesenteric artery strips tonin potentiates the effect of NE, almost doubling its response. A similar effect was observed on the KCl and AII-induced contraction. This tonin-induced potentiation is reversible and long-lasting, persisting for 1 to 2 hours after being added into the tissue bath. In 75% of the vascular strips assayed, tonin elicited a contraction with a short latency period and with a maximum tension ranging from a few milligrams to over 1 g. To clarify the mechanisms of tonin effect on vascular smooth muscle, a variety of agents have been used. Neither indomethacin, saralasin, nor alpha- or beta-adrenergic blockers changed the direct contraction or the potentiation induced to NE. Db-cAMP and theophylline blocked the potentiation to the response to NE. A Ca2+-free medium, La3+, and verapamil produced a 75% inhibition of the direct tonin-induced contraction. Papaverine, isoproterenol, and theophylline relaxed the same contraction. Enzymatic inactivation of tonin blocked completely the direct contraction but not the potentiation to NE. These experiments suggest that the vasoactive effect of tonin may be mediated by the release of intracellular-bound calcium, an effect dependent on a proteolytic effect of tonin, and by increasing the cellular permeability to calcium, which is not of a proteolytic effect. It is suggested that tonin remains attached to the vascular strips by mechanisms as yet not clarified.
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PMID:Effects of tonin, an angiotensin II-forming enzyme, on vascular smooth muscle in the normal rabbit. 626 53

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

Tonin, a new serine protease, found in high concentration in rat submaxillary glands, leads to a significant activation of human amniotic fluid renin. The optimum pH on renin activation by tonin was found at pH 6.0. The reaction was time dependent and the initial rate of angiotensin I generation was constant up to 2 h. The two amniontic fluid samples studied showed an increase in renin activity after incubation with tonin to about five times the control level (268 to 1240 pmol x h-1 x mL-1 and 1490 to 7480 pmol x h-1 x mL-1).
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PMID:Tonin as activator of renin. 629 10

There are two types of enzymes in tissues leading to angiotensin formation: a) those resulting in the formation of angiotensin I, such as renin and cathepsin D, the presence of which is now well established for brain tissue and b) Those leading to the direct formation of angiotensin II without the angiotensin I step, such as cathepsin G and tonin. Recent findings concerning tonin, a serine protease, are described: a) 80% of its amino acid sequence, b) its different characteristics from other serine proteases, from renin, cathepsin D and the angiotensin I converting enzyme, c) the activation of inactive renin, d) its involvement in the 1K-1C hypertensive rats, e) the demonstration of its presence in the distal tubular cells of the rat kidney, and finally, f) its presence in urine and the influence of age and of sodium intake on its urinary excretion.
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PMID:Extrarenal angiotensin-forming enzymes. 631 65

Tonin, an esteroprotease isolated from rat submaxillary gland, is a serine protease with trypsin- and chymotrypsin-like activity. The substrate specificity of tonin shows that it differs from kallikreins and is definitely not a renin-like enzyme or an angiotensin-converting enzyme. Tonin can produce directly the vasoactive peptide angiotensin II, from angiotensin I, angiotensinogen and the synthetic tetradecapeptide substrate of renin by cleavage of a Phe-His bond. It has also been found to cleave some Phe and Arg bonds in various substrates such as beta-lipotropin (beta-LPH), adrenocorticotropin (ACTH), pro-opiomelanocortin (POMC) and substance P. Here we describe the complete amino acid sequence of rat submaxillary gland, tonin. Comparison of the sequence of 219 amino acids with other serine proteases, particularly kallikreins, gamma-subunit of nerve growth factor (NGF) and the recently described gamma-renin, reveals extensive similarities. More interestingly, it also reveals the substitution of an Asp residue always found in the serine protease active site triad (Asp, His, Ser) by a Leu residue. This unusual substitution does not seem to affect the proteolytic activity of the enzyme.
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PMID:Amino acid sequence of rat submaxillary tonin reveals similarities to serine proteases. 632 14

Pig pancreatic kallikrein liberates kallidin from kininogen, whereas trypsin releases bradykinin. Recently, both kallikrein and trypsin have been reported to convert inactive plasma renin to active renin. However, we found that at pH 6.0, trypsin generated an angiotensin II-like pressor substance from human plasma protein in the absence of converting enzyme. This has been isolated and found to have the same amino acid composition as angiotensin II. Thus, in vitro trypsin can directly liberate both the depressor, bradykinin, in weak alkaline conditions, and the pressor, angiotensin II, at weakly acidic pH, from the appropriate substrates. We have now investigated whether kallikrein--a serine protease like trypsin--also generates a pressor substance at weakly acidic pH. Our results demonstrate that it does. We therefore suggest that kallikrein may be involved in a direct link between the pressor and depressor systems and we propose the term 'kinin-tensin system' for this sort of one-enzyme system capable of generating both depressor and pressor substances.
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PMID:Ability of kallikrein to generate angiotensin II-like pressor substance and a proposed 'kinin-tensin enzyme system'. 690 24

Various facets of activation of inactive renin by acidification or cold exposure were investigated in normal human plasma. The acid activation obtained by titration was usually less than that by dialysis method, but varied from 41% to 122% of the latter. The acid phase of acid activation accounted for about 70% of the total activation achieved by the combined effects of the acid and alkaline phases on the average, and was not affected by any of the inhibitors for serine, thiol or carboxyl protease, whereas serine protease inhibitors suppressed the activation of both renin and plasma kallikrein in the alkaline phase of acid activation. A different mode of plasma kallikrein activation suggested some difference in the mechanism between the alkaline phase of acid activation and the cryoactivation. A part of cryoactivation of renin was independent of the action of plasma kallikrein. The renin activated by either acidification or cold exposure without concomitant activation of plasma kallikrein was reinactivated by the removal of pH and temperature, but recovered by repeating acidification or cold exposure. When active plasma kallikrein had been produced, it activated inactive renin irreversibly. It appears unlikely that irreversible activation of inactive renin is taking place in the normal circulation where practically no active plasma kallikrein is present.
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PMID:Activation and reinactivation of inactive renin in normal human plasma. 703 32


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