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)

The pressor enzyme renin (EC 3.4.99.19) was isolated in a pure and stable form from hog kidney by affinity chromatography on a pepstatin/agarose gel followed by three additional steps of conventional chromatography. Destruction of the enzyme by proteolysis during isolation was prevented by chemically eliminating proteases in extracts. The pure preparation was used for the characterization of this enzyme. Renin was found to be a glycoprotein containing glucosamine and possessing binding affinity to concanavalin A. Contrary to previous reports, pure renin is stable at neutral pH either at 4 or -20 degrees for 3 to 8 weeks. It has a molecular weight of 36,400 as determined by equilibrium ultracentrifugation, an isoelectric point of 5.2 and E1%1cm (280 nm) of 9.1. In contrast to crude preparations, the enzyme activity has a broad pH optimum between pH 5.5 and 7.0 for both hog angiotensinogen and the synthetic octapeptide substrate benzyloxycarbonyl-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser-beta-naphthylamide. The rate of formation of angiotensin I from hog angiotensinogen at pH 6.0 and 37 degrees was 267 microng/h/microng of renin, or 2000 Goldblatt units/mg of renin. For the synthetic fluorogenic octapeptide substrate benzyloxycarbonyl-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser-beta-naphthylamide, a Km of 33 micronM and a Vmax of 0.94 micronmol/h/mg of enzyme were obtained at pH 6.5 and 37 degrees.
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PMID:Pure Renin. Isolation from hog kidney and characterization. 1 12

Studies were performed to evaluate the effects of the chronic administration of furosemide on hydrogen and electrolyte excretion in dogs on a normal electrolyte diet and in the absence of electrolyte or volume depletion. Control daily excretion in five dogs averaged 64 meq for Na, 51 meq for K, 66 meq for Cl, and 17 meq for net H. Furosemide, 40 mg, in the drinking water 3 times daily was given for 4 days. On day 1 Na excretion averaged 128 meq, but thereafter was not significantly different from control levels. Over 4 days cumulative net H excretion increased 63.6 meq and plasma HCO3 rose 6.6 meq/liter. The same dogs were restudied by the same protocol except that, to obviate electrolyte depletion, NaCl and KCl were administered daily in quantities sufficient to replace urinary losses. All dogs remained in positive Na, K, and Cl balance. Body weight, hematocrit, plasma albumin, creatinine, and plasma renin activity were unchanged, indicating the absence of electrolyte or volume depletion. Nonetheless, cumulative net H excretion increased 61.2 meq and plasma HCO3 increased 4.3 meq/liter. Two adrenalectomized dogs receiving steroid replacement showed similar changes in net H excretion and plasma HCO3. These experiments suggest that chronic furosemide administration may enhance H excretion and generate alkalosis even in the absence of volume or electrolyte depletion and without increased aldosterone secretion.
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PMID:Effect of chronic furosemide administration on hydrogen and sodium excretion in the dog. 1 99

1 The beta-adrenoceptor blocking effects of penbutolol were compared with those of propranolol and a placebo in a double-blind trial involving six healthy volunteers. 2 Heart rate (HR), systolic blood pressure (SBP) and peak expiratory flow rate (PEFR) were measured at rest and during vigorous exercise before and at intervals up to 7 h after oral administration of the drugs. In addition, plasma renin activity (PRA) at rest and plasma levels of penbutolol and propranolol were determined. 3 Penbutolol proved to be a non-cardioselective beta-adrenoceptor blocking drug, antagonizing exercise-induced tachycardia, reducing exercise-induced increase in PEFR and decreasing PRA. The beta-adrenolytic potency of penbutolol was shown to be four-fold that of propranolol but the duration of its effect was similar. 4 The peak plasma level of penbutolol was reached 1 h after administration and its half-life was 4.5 h. 5 Comparison of plasma levels and biological activity of penbutolol revealed that after oral administration this drug is transformed into an active metabolite in man.
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PMID:Comparative beta-adrenoceptor blocking effects and pharmacokinetics of penbutolol and propranolol in man. 1 32

To examine the direct effects of dopamine on renin release, the in vitro rat kidney slice system, devoid of hemodynamic and humoral effects, was chosen. In the presence of an antioxidant, ascorbic acid (6 X 10(-4)M), a significant dose-related stimulation of renin release was observed with addition of 10(-5)M and higher concentrations of dopamine. When the monoamine oxidase inhibitor, pheniprazine (1 X 10(-5)M) was added, significant, dose-related stimulation of renin release was observed with 10(-8)M and higher concentrations of dopamine. Dopamine-induced renin release was not inhibited by the presence of the alpha-adrenergic antagonist, phentolamine (9 X 10(-4)M), the dopaminergic antagonist, haloperidol (5 X 10(-5)M) or the neural uptake inhibitor, cocaine (1 X 10(-5)M). However, the presence of the beta-adrenergic antagonist, propranolol (2 X 10(-4)M) completely inhibited dopamine-induced renin release. These studies indicate that dopamine can directly stimulate renin release in the absence of effects of hemodynamic factors, alterations in sodium metabolism or release of endogenous adrenergic agents. Further, this direct effect of dopamine on renin release appears to be mediated by an agonistic effect on the juxtaglomerular beta receptor rather than by the presence of a specific dopaminergic receptor for renin release.
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PMID:The effects of dopamine on renin release in vitro. 1 42

Because propranolol is contraindicated in some patients and since clonidine can decrease heart rate and renin release, clonidine was substituted for propranolol in 14 severely hypertensive minoxidil-treated outpatients. Clonidine induced weight loss which, since plasma concentrations were not suppressed, was not due to inhibition of release of antidiuretic hormone or renin. These endocrine interrelations were confirmed by later administration of clonidine to 4 of the subjects under controlled circumstances in our General Clinical Research Center. When substituted for propranolol, clonidine controlled blood pressure and heart rate in 8 of the 9 outpatients whose blood pressure had been previously well controlled. Clonidine and propranolol had additive antihypertensive effects in the other 5 patients. Thus, clonidine can substitute for propranolol or when added to the propranolol-vasodilator combination supply an additional blood pressure-lowering effects. This substitution or addition results in an increase in side effects. In addition, clonidine has a diuretic action under these circumstances by an unknown mechanism.
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PMID:Clonidine and the vasodilating beta blocker antihypertensive drug interaction. 1 12

The properties of aqueous solutions of synthetic renin substrate tetradecapeptide (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser) were examined through electrometric titrations, infrared and circular dichroism spectroscopy, and spectrofluorometry. Titration studies of angiotensin I (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu) were also made, whose results indicated a flexible folded conformation similar to that previously proposed for the octapeptide angiotensin II, with a possible additional beta turn at the C terminus. The experimental results of the tetradecapeptide study, associated with Chou and Fasman calculations and with an analysis of structure-activity relationships in renin substrates and competitive inhibitors, led to the proposal of a beta turn involving the His-Pro-Phe-His sequence of the tetradecapeptide. This beta turn would be stabilized by beta-antiparallel interaction between residues 3-4 and 10-12 and by electrostatic attraction between the N-terminal ammonium and C-terminal carboxylate groups and would be destabilized below pH 5 by electrostatic repulsion between His6 and His9. The capacity to assume this conformation is related to structural requirements for renin substrates and competitive inhibitors.
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PMID:Conformations of synthetic tetradecapeptide renin substrate and of angiotensin I in aqueous solution. 1 34

1 (t-Butyl-amino-3-ol-2-propyl) oximino-9 fluorene is a new beta2-adrenoceptor blocking agent with a pA2 of 9.23+/-0.25 on isolated trachea. 2 It provokes hypertension in normotensive rats and does not prevent arterial hypertension in SHR rats, although it does prevent the renin secretion normally induced by isoprenaline infusion.
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PMID:A potent new beta2-adrenoceptor blocking agent. 1 16

Pooled plasmas from normal or binephrectomized rats and perfusates of isolated livers were used as sources of renin substrate for isoelectric focusing. After desalting, preliminary fractionation (plasma only), and concentration, the preparations were focused in a pH 3--10 gradient on 20-cm glass plates layered with Sephadex slurry. The pH 4--6 region, containing all the substrate, was scraped from this plate and refocused in a pH 4--6 gradient. Substrate content of 1-cm strips of slurry from half of the plate was determined by both radioimmunoassay and bioassay of angiotensin resulting from incubation with added renin. Corresponding strips from the other half of the plate were incubated without renin as a control for any preformed angiotensin. The asymmetry and broad distribution (pH 4--5) of substrate from different sources suggested the existence of more than one form. Higher resolution achieved by using the high substrate concentration of postnephrectomy plasma and 0.5-cm strips of slurry on 20-cm or 40-cm plates revealed peaks and shoulders of substrate activity. Our data suggest that multiple forms of substrate are synthesized by the liver and circulate in plasma. Postnephrectomy rat plasma appears to contain relatively more substrate(s) with higher isoelectric points than in normal plasma, possibly an accumulation of forms ordinarily degraded by endogenous renal renin.
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PMID:Resolution of rat renin substrates by isoelectric focusing. 1 43

1. Inactive renin, which can be converted into an active form by acidification to pH 3-3, represents 4-63% of the total renin in rat peripheral plasma. 2. No inactive component could be found in the blood-free venous effluent of the perfused rat kidney before and after stimulation with isoprenaline. 3. This suggests a possible extrarenal source for inactive renin and may explain the presence of this component in anephric patients.
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PMID:Evidence that 'inactive' renin is produced outside the kidney of the rat. 1 91

Essential hypertension (EH) can be subdivided according to the sympathetic and renin activity into two contrasting forms: (1) borderline beta-hyperadrenergic renin hyperresponsive and (2) stable beta-hypoadrenergic renin hyporesponsive EH. These two forms probably represent two expreme poles in the spectrum of EH in which sympathetic and renin hyper- or hyporeactivity cannot be accounted for by catecholamine determinations solely. beta-Adrenergic responsiveness monitored by plasma cyclic AMP determinations revealed plasma cyclic AMP, renin and circulatory hyperresponsiveness to isoproterenol in borderline hyperadrenergic EH while the opposite, cyclic AMP and renin hyporesponsiveness to insulin-induced hypoglycemia have been described in low renin stable EH. The kidney is in the center of the adrenergic abnormality in the two forms of EH with the borderline one excreting into the urine catecholamines not accounted for by their glomerular filtration. Catecholamines solely, however, do not account for the differences in both forms of EH which can probably be attributed to their different beta-adrenergic responsiveness.
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PMID:Catecholamines, cyclic AMP and renin in two contrasting forms of essential hypertension. 1 3


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