Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The two equilibrium constants that define the extent of carbamino adduct formation with amines for all values of pH and PCO2 are determined for the alpha-amino groups of the peptide hormones angiotensin II(AII) and bradykinin (BK) by nuclear magnetic resonance techniques. From these constants the variation of carbamino adduct formation has been calculated over the pH range 6.60--8.00 with variable PCO2, and the results are superimposed upon standard pH-bicarbonate diagrams. PCO2, and the results are superimposed upon standard pH-bicarbonate diagrams. The mole fraction, Z, of carbamino adduct form of AII or BK shows a maximum variation in going from metabolic alkalosis, Z congruent to 0.30, to metabolic acidosis, Z congruent to 0.02, with Z near 0.2 for normal acid-base conditions. Adduct formation to hormone may alter the biological effect of the hormone (a) by limiting proteolysis, particularly at the amino-terminal, (b) by altering hormone binding affinity to specific receptors, or (c) by converting the hormone to an antagonist which binds to receptor but does not activate subsequent metabolic events. The requirements for any of these mechanisms to operate are examined in terms of simple equilibrium considerations, and experimental evidence of inhibition of an aminopeptidase model system is presented. These results are consistent with the hypothesis that regulation of some physiological processes through formation of carbamino adduct of peptide hormones is possible.
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PMID:The quantitation of carbamino adduct formation of angiotensin II and bradykinin. 3 35

Angiotensin-converting enzyme has been solubilized from a particulate fraction of rabbit lung and purified to apparent homogeneity in 11% yield by a procedure including fractionation with DEAE-cellulose and calcium phosphate gel, elution from Sephadex G-200, and lectin affinity chromatography. The molecular weight estimated by equilibrium sedimentation was approximately 129,000, either in the absence or presence of 6 M guanidine hydrochloride. A slightly higher value of 140,000 determined for the reduced, denatured protein by gel electrophoresis in the presence of sodium dodecyl sulfate and a much higher figure derived from gel filtration are probably due to the glycoprotein nature of the enzyme. Its oligosaccharide content accounted for 26% of the weight calculated from its amino acid and carbohydrate composition. The estimated content of sugar residues per mole was: galactose, 57; N-acetylglucosamine, 53; mannose, 43; N-acetylneuraminic acid, 19; and fucose, 4. Threonine and alanine were identified, respectively, as NH2-terminal and COOH-terminal residues by the dansylation procedure and by digestion with carboxypeptidase A. The enzyme was found to contain approximately 1 g atom of zinc per mol. Km values for hydrolysis of hippurylhistidylleucine and angiotensin I were 2.3 and 0.07 mM, and the corresponding turnover numbers were 15,430 and 792 mol/min/mol at 37 degrees. Bradykinin was also a substrate, and release of its COOH-terminal dipeptide, Phe-Arg, was catalyzed at a comparable rate to that of His-Leu from the COOH terminus of angiotensin I. Enzyme activity required the presence of chloride ions and was inhibited by EDTA and by low concentrations of Bothrops bradykinin-potentiating peptides. In addition, hydrolysis of hippurylhistidylleucine was inhibited competitively by other defined peptides, including di- and tripeptides, which were not substrates.
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PMID:Pulmonary angiotensin-converting enzyme. Structural and catalytic properties. 16 57

Investigations on various kinds of biological actions of a newly purified hypothalamic tridecapeptide, neurotensin, were performed both in vivo and in vitro by utilizing experimental animal models. The effect of neurotensin on pituitary gonadotropin release was studied in ovariectomized estrogen-progesterone-treated rats by the measurement of serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL) in radioimmunoassays. Neurotensin (340 mg/100 g BW) significantly increased serum LH and FSH 30 minutes after an intravenous injection (p smaller than 0.05) and lowered serum prolactin concentrations significantly (p less than 0.025). Bradykinin and substance P showed on significant effect on serum LH and FSH release. Intraperitoneal or intravenous administration of 0.5 n.mole neurotensin lowered blood pressure in intact mature rats from the range of 90 approximately 100 mmHg to 50 approximately 60 mmHg; however, tachyphylaxis was observed after repeated injections of the same dose of this peptide. Neurotensin was as potent as bradykinin in inducing rat duodenum relaxation and guinea pig ileum contraction in vitro. Theses effects on neurotensin and bradykinin on the intestines were not inhibited by the pre-treatment of phentolamine, propranolol, methysergide and pyribenzamine. Bradykinin induced contractions of the uterus in proestrous rats, but neurotensin induced no marked contraction. These results suggest that neurotensin in not hypothalamic releasing or inhibiting factor but possess the nature of kinin.
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PMID:[A study on the biological action of hypothalamic tridecapeptide, neurotensin (author's transl)]. 43 7

1. Intracranial injections of the individual components of the renin-angiotensin system caused drinking in water-replete dogs. 2. Angiotensin II was the most reliable, potent and rapidly acting intracranial dipsogen and elicited drinking in the absence of peripheral circulatory changes. After the highest dose of angiotensin II (10(-9) mole) five dogs drank a mean amount of 380.0 +/- 88.6 ml. For the other components, the order of dipsogenic effectiveness was angiotensin I, synthetic renin substrate, and angiotensin III. 3. Isotonic saline, bradykinin (10(-10) mole), eledosin-hexapeptide (10(-10) mole), oxytocin (10(-10) mole) and prostaglandin F2alpha (1-200 X 10(-12) mole) were ineffective. 4. Intracranial renin (10 m-u.) produced a mean intake of 445 +/- 152 ml. of water in eight dogs. 5. Dog renin substrate and synthetic renin substrate, injected intracranially in a dose of 10(-10) mole, produced similar intakes of water but these amounts were very much less than the volume drunk in response to the same dose of angiotensin II. 6. None of the components injected into dipsogenically responsive sites in the brain caused changes in blood pressure, although the act of drinking itself produced a small rise. 7. Angiotensin II at the highest dose produced drinking when injected into the subfornical organ, preoptic region, anterior hypothalamus, lateral ventricle, third ventricle, ventral hippocampus and mid-line thalamus. Negative sites were found in the caudate nucleus, fourth ventricle, mid-brain, posterior thalamus, dorsal hippocampus, lateral hypothalamus and posterior hypothalamus. 8. After the lowest dose of intracranial angiotensin II (10(-12) mole) only the preoptic region and subfornical orgal were responsive. These two sites were equally sensitive in terms of latency and amounts drunk at all doses injected. 9. Angiotensin did not necessarily have to reach a cerebral ventricle in order to cause drinking. 10. The dog resembles the rat in its responsiveness to the dipsogenic action of intracranial angiotensin II. The regions of the brain from which drinking can be elicited are more widespread than has been claimed by some in the rat.
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PMID:Drinking and haemodynamic changes induced in the dog by intracranial injection of components of the renin-angiotensin system. 65 Apr 66

The relationship between bronchial edema and airway responsiveness was studied in cats in situ. Five cats were exsanguinated, and the bronchial arteries were perfused. We monitored pulmonary resistance (RL), and the provocative dose of acetylcholine (ACh) required to produce a 300% increase in RL (PD300) was determined. Bronchial vascular permeability was measured by quantifying extravasation of Evans blue (EB) dye. Bradykinin (BK) and ACh were administered via the bronchial arteries to increase leakage and bronchoconstriction, respectively. BK preperfusion (for 30 min) significantly increased bronchial vascular permeability to four times the control values (p < 0.05). BK preperfusion did not alter baseline RL but caused hyperresponsiveness to ACh, with log [PD300 (mole)] of -6.53 +/- 0.42 (mean +/- SD) and -6.90 +/- 0.30, before and after BK, respectively (p < 0.01). Furthermore, the maximal airway narrowing after BK was 58% higher than before BK (p < 0.01). Histologic study showed peribronchial edema after BK. The enhancement of maximal airway narrowing was significantly correlated with the degree of EB dye extravasation. These results suggest that BK causes airway hyperresponsiveness to ACh and increases maximal airway narrowing, possibly because of airway edema.
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PMID:Bradykinin causes airway hyperresponsiveness and enhances maximal airway narrowing. Role of microvascular leakage and airway edema. 144 87

Degradation of bradykinin and lysylbradykinin was studied in plasma and serum, and the results were compared to those seen with mixtures of carboxypeptidase N and angiotensin-converting enzyme (ACE), the two recognized kininases in blood. Angiotensin-converting enzyme was an effective kininase in mixtures with carboxypeptidase N at physiologic concentration and digested bradykinin to the dipeptides Phe- Arg and Ser-Pro plus the pentapeptide Arg-Pro-Pro-Gly-Phe. Carboxypeptidase N slowly removed the C-terminal Arg from bradykinin to yield des-Arg9-bradykinin (DBK); the latter was digested by ACE to yield the aforementioned pentapeptide and the tripeptide Ser-Pro-Phe. In serum, however, the C-terminal Arg was removed from bradykinin about five times faster than was accounted for by the activity of carboxypeptidase N. The primary substrate of ACE in serum, therefore, was des-Arg9-bradykinin and not bradykinin. The products of this reaction, pentapeptide and tripeptide, were unstable in serum and were cleaved by enzymes that have not yet been characterized. One product, free phenylalanine, was used to monitor these reactions by HPLC. Our studies indicate that the final products of bradykinin degradation were the tripeptide Arg-Pro-Pro, one mole each of Ser, Pro, Gly, and Arg, and two moles of phenylalanine. Since the serum level of carboxypeptidase N did not account for the rapid kinin degradation seen, other carboxypeptidases may have been operative, perhaps released as a result of blood clotting, or a serum cofactor may augment carboxypeptidase N activity.
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PMID:Mechanism of digestion of bradykinin and lysylbradykinin (kallidin) in human serum. Role of carboxypeptidase, angiotensin-converting enzyme and determination of final degradation products. 253 65

Bradykinin (BK) receptor of uterus and chorionic membrane were studied by radioreceptor assay to clarify the role of BK as theta an agent contracting uterine muscle. Basic examination revealed that incubation at 0 degrees C for 45 minutes with [3H] BK in buffer containing 5mM Mg++ was the most suitable condition for receptor-BK binding. BK receptor assay of several kinds of tissue such as pregnant rat uterus, human chorionic membrane, and placenta was done and the following results were obtained. Specific BK receptor existed in human chorionic membrane and in rat uterus. Ultracentrifugation revealed that it was on the plasma membrane (145 f mole./mg protein: The highest binding in the pellet at 10,000 g centrifugation followed by 600 g centrifugation). Association constant (Ka) and maximal binding capacity (MBC) showed the lowest level at 15 days gestation in rat uterus. These seemed to effectively maintain pregnancy by inhibiting uterine contraction. Both Ka and MBC were increased in the uterus of intrapartum rat compared with that of prepartum, but the former was about 45%, and the latter was almost the same as, that of non pregnant rat.
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PMID:[Bradykinin receptor and the mechanism of the onset of labor]. 287 81

Two species of T-kininogen which release T-kinin (Ile-Ser-bradykinin) have been purified from plasma of rats treated with Freund's complete adjuvant. The molecular weight was estimated to be 69,000 for either T-kininogen I and II by SDS-polyacrylamide gel electrophoresis. Trypsin released one mole of T-kinin from one mole of either T-kininogen, but glandular kallikrein, including rat urinary and rat submandibular gland kallikreins and human urinary kallikrein, did not release any kinin from T-kininogens. Cathepsin D, which was purified from rat liver, released T-kinin from T-kininogens at pH 4.0. These results indicate that rat plasma contains two types of T-kininogen which differ from high molecular weight and low molecular weight kininogens.
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PMID:Isolation and properties of two rat plasma T-kininogens. 354 20

1. When applied directly to the brain, angiotensin II amide, as either the valine(5) octapeptide, causes rats in normal fluid balance to drink water.2. The drinking response to angiotensin injections is copious, rapid, repeatable within the same test session, and stable over months of testing in the same animal.3. The response is motivationally potent and specific. After injection the animals move directly to the source of water and drink. There is typically no preliminary hyperactivity or subsequent depression. The animals do not eat, gnaw or exhibit other behaviours that are not normally seen during spontaneous drinking. The injections rouse sleeping animals to drink and interrupt eating in animals deprived of food for two days.4. The region of the brain that is most sensitive to angiotensin includes the anterior hypothalamus, the preoptic region, and the septum including the nucleus accumbens.5. Intracranial renin elicited drinking. Bradykinin and vasopressin did not, nor did adrenaline, noradrenaline or aldosterone. In the most sensitive region, sites positive for angiotensin also yielded drinking to carbachol.6. Responses were obtained with 5 ng (ca. 5 p-mole) and occurred reliably with 50 ng angiotensin or more. The dose-response curve for amount drunk rose from 5 to 100 ng and levelled off thereafter. Angiotensin is therefore the most potent dipsogen known and is effective at doses that are reasonably within the concentration range for circulating endogenous angiotensin.7. Injections into the sensitive region of doses of angiotensin that were effective for drinking did not produce peripheral haemodynamic changes in lightly anaesthetized rats.8. This work strengthens the suggestion that angiotensin is a natural hormone of drinking behaviour that participates in extracellular thirst by its release from the kidney and subsequent direct action on a specific chemoreceptive region in the anterior diencephalon and limbic lobe.
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PMID:Drinking induced by injection of angiotensin into the rain of the rat. 432 23

Concentrations of butylated hydroxyanisole as low as 8 x 10(-9) mole per liter can inhibit detectably the contraction of smooth muscle elicited by bradykinin. The mechanism of the inhibitory effect of this food grade anti-oxidant is apparently complex, and the effect is only partially reversible.
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PMID:Bradykinin inhibition by butylated hydroxyanisole. 541 50


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