Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Isoelectric focusing studies of human placental diamine oxidase showed the pI value of the active enzyme to be 6.5. This information was used in modifying the enzyme purification by incorporating column chromatography on DEAE-Sephadex with ionic strength and pH gradient elution and this, together with affinity chromatography on concanavalin A--Sepharose, gave a highly purified preparation, with a specific activity of 7.0 units/mg. 2. The enzyme gave the expected stoicheiometry with p-dimethylaminomethylbenzylamine as substrate (Keq. 2700) and also oxidized [8-arginine]vasopressin, [8-lysine]vasopressin, collagen and tropocollagen. Polyacrylamide gel slices showed identical migration of diamine-oxidizing and [8-lysine]vasopressin-oxidizing activity. 3. The molecular weight, determined by ultracentrifugation, sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, variable polyacrylamide-gel electrophoresis and Sephadex G-200 column chromatography, was estimated to be approx. 70000. 4. E.s.r. spectroscopy showed that copper and manganese were present in the purified enzyme. This result was confirmed by atomic absorption spectroscopy, which indicated a stoicheiometry for copper and manganese of approx. 1.0 and 1.2g-atom respectively/70000mol.wt. unit. 5. The e.s.r. spectral intensity did not decrease nor did the spectral line shape change when excess of p-dimethylaminomethylbenzylamine was added to the enzyme. 6. Addition of K13CN to the enzyme eliminated the copper e.s.r. signal without affecting the manganese signal. 7. The placental enzyme therefore appears to differ from other amine oxidases in terms of its metal cofactor requirement, molecular weight and substrate specificity, and possible roles in vivo for this enzyme are discussed.
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PMID:Human placental diamine oxidase. Improved purification and characterization of a copper- and manganese-containing amine oxidase with novel substrate specificity. 18 34

Whereas adenosine itself exerted independent stimulatory and inhibitory effects on the adenylate cyclase activity of a platelet particulate fraction at low and high concentrations respectively, 2-substituted and N6-monosubstituted adenosines had stimulatory but greatly decreased inhibitory effects. Deoxyadenosines, on the other hand, had enhanced inhibitory but no stimulatory effects. The most potent inhibitors found were, in order of increasing activity, 9-(tetrahydro-2-furyl)adenine (SQ 22536), 2',5'-dideoxyadenosine and 2'-deoxyadenosine 3'-monophosphate. Kinetic studies on prostaglandin E1-activated adenylate cyclase showed that the inhibition caused by either 2',5'-dideoxyadenosine or compound SQ 22536 was non-competitive with MgATP and that the former compound, at least, showed negative co-operativity; 50% inhibition was observed with 4 micron-2',5'-dideoxyadenosine or 13 micron-SQ 22536. These two compounds also inhibited both the basal and prostaglandin E1-activated adenylate cyclase activities of intact platelets, when these were measured as the increases in cyclic [3H]AMP in platelets that had been labelled with [3H]adenine and were then incubated briefly with papaverine or papaverine and prostaglandin E1. Both compounds, but particularly 2',5'-dideoxyadenosine, markedly decreased the inhibition by prostaglandin E1 of platelet aggregation induced by ADP or [arginine]vasopressin as well as the associated increases in platelet cyclic AMP, so providing further evidence that the effects of prostaglandin E1 on platelet aggregation are mediated by cyclic AMP. 2'-Deoxyadenosine 3'-monophosphate did not affect the inhibition of aggregation by prostaglandin E1, suggesting that the site of action of deoxyadenosine derivatives on adenylate cyclase is intracellular. Neither 2',5'-dideoxyadenosine nor compound SQ 22536 alone induced platelet aggregation. Moreover, neither compound potentiated platelet aggregation or the platelet release reaction when suboptimal concentrations of ADP, [arginine]vasopressin, collagen or arachidonate were added to heparinized or citrated platelet-rich plasma in the absence of prostaglandin E1. These results show that cyclic AMP plays no significant role in the responses of platelets to aggregating agents in the absence of compounds that increase the platelet cyclic AMP concentration above the resting value.
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PMID:Inhibition of adenylate cyclase by adenosine analogues in preparations of broken and intact human platelets. Evidence for the unidirectional control of platelet function by cyclic AMP. 21 36

Platelet behaviour was studied in groups of women suffering from mild and severe pre-eclampsia, and compared with normal pregnant and non-pregnant controls. Platelets from women with severe pre-eclampsia were less responsive than normal to a variety of aggregating agents, and this impairment was significant in response to collagen and vasopressin. Women with severe pre-eclampsia had raised plasma adenine nucleotide levels and lowered platelet 5-hydroxytryptamine levels compared with the controls. Platelets from women with mild pre-eclampsia showed only a slight difference from normal. These findings may be the result of platelets having undergone aggregation and disaggregation within the circulation, and suggest that platelets may be involved in the pathogenesis of pre-eclampsia.
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PMID:Abnormal platelet function in pre-eclampsia. 62 22

Platelets lose their ability to aggregate when deprived of divalent cations. This usually was studied by incubating human citrated platelet-rich plasma with EDTA or EGTA and then adding enough CaCl2 to combine with the chelating agent. Incubation for 5-7 min at 37 degrees C caused irreversible loss of the platelets' ability to adhere to glass and to aggregate with ADP, epinephrine, A23187, vasopressin, or serotonin or upon rewarming after chilling and markedly reduced aggregation with collagen or thrombin. Control samples incubated with saline, CaEDTA, or CaEGTA were not inhibited. Untreated platelets washed and incubated in solutions treated with resins that remove divalent cations lost their ability to aggregate in 30 min. More than about 0.26 mM Mg2+ partially protected the platelets. Unlike aggregation, ADP-induced shape change, clot retraction caused by thrombin or ADP plus reptilase, and thrombin-induced 14C-serotonin release were not inhibited after incubation. Aggregability was not restored by prolonged incubation with CaCl2, adding normal plasma, or washing the platelets. Its loss was temperature and pH dependent, occurring in 2 min at 43 degrees C but not in 7 min at 30 degrees C, and at pH 7.8 but much less at pH 7.2. The defect was not associated with an increase in platelet cyclic AMP, a decrease in metabolic ATP, or the presence of free ADP.
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PMID:Nonreversible loss of platelet aggregability induced by calcium deprivation. 67 68

1. The 2',3'-dialdehyde derivative of ADP (oADP) at concentrations approaching the millimolar range induces human blood platelets to undergo the transition from discoid to globular morphology (the 'shape change') but is incapable of inducing aggregation. 2. When incubated with platelets for 1 min before addition of the agonist, oADP acts as a competitive inhibitor of shape change and aggregation induced by ADP. Under these conditions secretion and hence aggregation induced by low concentrations of collagen; and secretion and hence secondary aggregation induced by adrenaline, thrombin and vasopressin are also inhibited by this analogue. In addition, oADP stimulates the rate of primary aggregation induced by adrenaline and causes partial inhibition of primary aggregation induced by thrombin or vasopressin. When longer preincubation times are employed the extent of inhibition with respect to all agonists, except for high concentrations of collagen, is increased and the competitive character of the inhibition with respect to ADP is no longer apparent. 3. Incubation of human platelets with the 2',3'-dialdehyde derivative of ATP (oATP) causes effects similar to those described for oADP except that the analogue neither induces platelet shape change, nor stimulates the rate of primary aggregation induced by adrenaline. In addition oATP fails to cause significant inhibition of platelet shape change induced by serotonin. The extent and character of inhibition caused by addition of oATP is not a function of the time of incubation. 4. The 2',3'-dialcohol derivatives of ADP and ATP and orATP) effect the aggregation properties of human blood platelets in a manner generally resembling those observed for the 2',3'-dialdehyde analogues. However, orADP is only weakly effective in causing platelet shape change and stimulating the rate of primary aggregation induced by adrenaline and does not inhibit secretion induced by adrenaline, collagen, thrombin and vasopressin. The extent of inhibition by orADP increases only slightly with increased time of incubation. 5. The data suggest that oADP acts as a partial agonist, and oATP as an antagonist, at the platelet ADP receptor, but that platelet membrane stabilisation also results from interaction with these dialdehyde analogues. Such membrane stabilisation does not complicate the interaction of platelets with orADP, which appears to act as a classical antagonist for the ADP receptor.
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PMID:Interaction of human blood platelets with the 2',3'-dialdehyde and 2',3'-dialcohol derivatives of adenosine 5'-diphosphate and adenosine 5'-triphosphate. 68 37

Investigations effected in 16 subjects of 20-69 years at bed rest after bone fractures demonstrated, in an interval of 10-27 days after surgery, normal plasma sodium concentration and a decreased urinary elimination, an increased plasma potassium concentration but a decreased urinary output. The osmotic changes were not significant. The plasma vasopressin activity was increased. Three urinary aldosterone determinations showed an increased output. The serum calcium level was within normal limits but its urinary output was initially slightly decreased, contrary to its augmented elimination after simple voluntary bed rest, as results from literature. The hydroxyproline elimination was increased, demonstrating an active collagen metabolism.
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PMID:Hydroelectrolytic changes caused by prolonged clinical recumbency. 81 41

High concentrations of cephalothin or penicillin G inhibit a number of the functions of human or rabbit platelets in citrated platelet-rich plasma (PRP) and in suspensions of washed platelets. The reactions shown to be inhibited are: ADP-induced shape change and the primary and secondary phases of aggregation and release induced by ADP or adrenaline in human cirtated PRP; release and aggregation of washed human platelets exposed to collagen, thrombin, vasopressin, or the ionophore A 23,187; aggregation of washed human platelets exposed to phytohaemagglutinin from Phaseolus vulgaris (PHA) or polylysine; release induced by concanavalin A or PHA in suspensions of washed platelets from rabbits; platelet adherence to a collagen-coated surface or to the damaged intimal surface of the rabbit aorta; platelet factor 3 availability; lysis of rabbit platelets by an antiserum directed against them; and clot retraction. Neither antibiotic affected serotonin-induced aggregation; a high concentration of cephalothin slightly inhibited the initial rate of serotonin uptake. Penicilloic acid showed about half the inhibitory effect of penicillin G on ADP-induced aggregation. In citrated human platelet-rich plasma, ampicillin and oxacillin inhibited ADP-induced aggregation to the same extent as similar concentrations of penicillin G; in suspensions of washed platelets, however, ampicillin was less inhibitory than penicillin G or oxacillin. Platelet ultrastructure, assessed by transmission electron microscopy, was not visibly altered. Evidence that the antibiotics become bound to platelets is the finding that platelets incubated with the antibiotics ans resuspended in fresh media showed less response to aggregating agents compared with control platelets. Penicillin G and related antibiotics may be inhibitory because they coat the platelet surface. Their effects on platelet functions are probably responsible for excessive bleeding and increased bleeding times observed in patients and volunteers receiving high doses of these antibiotics.
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PMID:Effects of cephalothin and penicillin G on platelet function in vitro. 86 92

The thrombocyte membrane is characterized by several pecularities, first by its morphology which includes deep invaginations into the interior of the cell and, second, by its capacity to become stimulated by a wide variety of seemingly unrelated external agents which extend from proteases to collagen, certain immune complexes and small molecular weight substances such as ADP, adrenaline, serotonin and vasopressin. The response of the membrane to stimulation consists in a drastic rearrangement of its constituents, as exemplified by the appearance on the outer surface of components which are not accessible in the resting platelet. Stimulation may either lead to morphological changes and to aggregation or to more far-reaching alterations linked to aggregation, namely the release of substances from storage organelles and manifestations of gross contractile activity. The generation of these sequential reactions involves the production, by the exited membrane of a hitherto ill-defined signal to the interior of the cell. One of the most important consequences of this signal consists in the release, from internal sources, of calcium ions. Calcium ions are directly involved in the rapid shape change of stimulated platelets, due to their depolymerizing effect on the microtubules, they furthermore trigger the release reaction, in which the prostaglandin in system seems also to be involved and, finally, they are essential for the activation of the contractile system. Simultaneous with the release reaction, the platelet plasma membrane acquires calcium permeability; hence, in a later phase, cytoplasmic calcium originates not only from internal sources, but also from the surrounding medium. It is particularly noteworthy that all these alterations of the plasma membrane are reversible, which means that not only the essential structural rearrangements which occur upon stimulation in the membrane are reversed but also that the cell is capable of removing the Ca2+-ions which have entered the cytoplasm during the activation phase.
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PMID:[The thrombocyte membrane]. 100 58

Experimental myocardial infarction is a model of cardiac overload due to amputation of part of the cardiac muscle. The development of cardiac failure depends on the size of the infarct and the time factor. This model of overload is associated with changes of the phenotype of the remaining healthy muscle and with peripheral vascular modifications partially dependent of the activation of pressor and/or deactivation of dilator systems. These changes are proportional to the size of the infarction at a given time after induction of the model. The degree of right ventricular hypertrophy and the decrease in blood pressure reflect the severity of infarction and the deterioration of the remaining myocardial function, affecting the haemodynamics both before and after the left ventricle. The increases in the 1/3 forms of isomyosins, the amount of subendocardial collagen, the biosynthesis, stocking and secretion of ANF are related to the infarct size and degree of overload. Similarly, the concentration of cyclic GMP is proportional to the infarct size. These parameters reflect ventricular overload, the increase of stress and energy deprivation of the remaining healthy muscle. The activation of peripheral pressor systems is also dependent on the infarct size reflects the effect of cardiac pump dysfunction on the kidney, liver, brain and endothelium. Large infarcts are associated with increased circulating renin and renal concentrations, with a decrease in angiotensinogen levels related to its consumption by the renin and to reduced hepatic synthesis and also with increased secretion and biosynthesis of vasopressin by the hypothalamus. In this model, Perindopril is beneficial by decreasing the cardiac load. It reduces the blood pressure, causes regression of bi-auricular and right ventricular hypertrophy. Changes in myosin isoenzyme configuration regress and subendocardial fibrosis and ANF concentrations are normalised. The effects of ACE inhibitors in this context, though very beneficial, are limited by the impossibility of normalising cardiac load and stress when the initial amputation of cardiac contractile mass exceeds 40%.
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PMID:[Experimental myocardial infarction in the rat. Effect of perindopril]. 166 27

Platelets respond through discrete receptors to a number of physiological stimuli and foreign surfaces with a sequence of measurable responses: shape change, aggregation, secretion and arachidonate liberation. Three secretory responses are distinguished: release of substances from 1) dense granules (ADP, serotonin), 2) alpha-granules (coagulation factors, platelet-specific proteins, adhesive proteins) and 3) lysosomes (acid hydrolases). The liberated arachidonate is converted to prostaglandins and thromboxanes which, together with secreted ADP and close cell contact, will cause further platelet activation through "positive feedback" (autocrine stimulation). Some agonists are "weak" (ADP, vasopressin, platelet-activating factor) and depend on positive feedback to promote the full sequence of responses, while other agonists are "strong" (thrombin, collagen) and stimulate the entire response sequence without positive feedback. Most agonists appear to stimulate platelet responses via G-protein-dependent activation of phospholipase C, resulting in diesteratic hydrolysis of phosphatidylinositol-4,5-bisphosphate yielding inositol-1,4,5-trisphosphate and diacylglycerol. These are signal molecules which mobilize cytoplasmic Ca2+ and stimulate protein kinase C, respectively. Cytoplasmic Ca2+ will in turn activate protein phosphorylations which eventually lead to execution of the various responses while activation of protein kinase C appears to be linked to regulation of intracellular pH through Na+/H+ exchanger and to termination of the Ca(2+)-mediated signal processing. Other agonists (prostaglandins I2 and D2) counteract platelet stimulation through classical activation of adenylate cyclase.
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PMID:Signal transducing mechanisms in platelets. 166 17


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