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

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.
 ...
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.
 ...
PMID:[A study on the biological action of hypothalamic tridecapeptide, neurotensin (author's transl)]. 43 7

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.
 ...
PMID:Bradykinin causes airway hyperresponsiveness and enhances maximal airway narrowing. Role of microvascular leakage and airway edema. 144 87

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.
 ...
PMID:[Bradykinin receptor and the mechanism of the onset of labor]. 287 81

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.
 ...
PMID:Drinking induced by injection of angiotensin into the rain of the rat. 432 23

Regulatory mechanisms in bradykinin (BK) activated release of arachidonate (ARA) and synthesis of prostaglandin (PG) and platelet activating factor (PAF) were studied in bovine pulmonary artery endothelial cells (BPAEC). A role for GTP binding protein (G-protein) in the binding of BK to the cells was determined. Guanosine 5-O- (thiotriphosphate), (GTPtauS), lowered the binding affinity for BK and increased the Kd for the binding from 0.45 to 1.99 nM. The Bmax remained unaltered at 2.25 x 10(-11) mole. Exposure of the cells to aluminium fluoride also reduced the affinity for BK. Bradykinin-induced release of ARA proved pertussis toxin (PTX) sensitive, with a maximum sensitivity at 10 ug/ml PTX. GTPtauS at 100 muM increased the release of arachidonate. The effect of GTPtauS and BK was additive at suboptimal doses of BK up to 0.5 nM but never exceeded the levels of maximal BK stimulation at 50 nM. PTX also inhibited the release of ARA induced by the calcium ionophore, A23187. Phorbol 12-myristate 13-acetate or more commonly known as tetradecanoyl phorbol acetate (TPA) itself had little effect on release by the intact cells. However, at 100 nM it augmented the BK activated release. This was downregulated by overnight exposure to TPA and correlated with down-regulation of protein kinase C (PKC) activity. The down-regulation only affected the augmentation of ARA release by TPA but not the original BK activated release. TPA displayed a similar, but more potent amplification of PAF synthesis in response to both BK or the calcium ionophore A23187. These results taken together point to the participation of G-protein in the binding of BK to BPAEC and its activation of ARA release. Possibly two types of G-protein are involved, one associated with the receptor, the other activated by Ca(2+) and perhaps associated with phospholipase A(2) (PLA(2)). Our results further suggest that a separate route of activation, probably also PLA(2) related, takes place through a PKC catalysed phosphorylation.
 ...
PMID:Mechanisms in bradykinin stimulated arachidonate release and synthesis of prostaglandin and platelet activating factor. 1847 53