Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:031673 (collagen)
 124,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities of adenylate and guanylate cyclase and cyclic nucleotide 3':5'-phosphodiesterase were determined during the aggregation of human blood platelets with thrombin, ADP, arachidonic acid and epinephrine. The activity of guanylate cyclase is altered to a much larger degree than adenylate cyclase, while cyclic nucleotide phosphodiesterease activity remains unchanged. During the early phases of thrombin-and ADP-induced platelet aggregation a marked activation of the guanylate cyclase occurs whereas aggregation induced by arachidonic acid or epinephrine results in a rapid diminution of this activity. In all four cases, the adenylate cyclase activity is only slightly decreased when examined under identical conditions. Platelet aggregation induced by a wide variety of aggregating agents including collagen and platelet isoantibodies results in the "release" of only small amounts (1-3%) of guanylate cyclase and cyclic nucleotide phosphodiesterase and no adenylate cyclase. The guanylate cyclase and cyclic nucleotide phosphodiesterase activities are associated almost entirely with the soluble cytoplasmic fraction of the platelet, while the adenylate cyclase if found exclusively in a membrane bound form. ADP and epinephrine moderately inhibit guanylate and adenylate cyclase in subcellular preparations, while arachidonic and other unsaturated fatty acids moderately stimulate (2-4-fold) the former. It is concluded that (1) the activity of platelet guanylate cyclase during aggregation depends on the nature and mode of action of the inducing agent, (2) the activity of the membrnae adenylate cyclase during aggregation is independent of the aggregating agent and is associated with a reduction of activity and (3) cyclic nucleotide phosphodiesterase remains unchanged during the process of platelet aggregation and release. Furthermore, these observations suggest a role for unsaturated fatty acids in the control of intracellular cyclic GMP levels.
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PMID:Cyclic nucleotides and platelet aggregation. Effect of aggregating agents on the activity of cyclic nucleotide-metabolizing enzymes. 0 49

The in vitro effects of N-3-(1-benzyl-cycloheptyloxy)-propyl-N,N-dimethylammonium-hydrogenfumarate (bencyclan) on clotting, fibrinolytic and platelet function test were investigated by adding the drug to normal human plasma. An anticoagulant activity, mainly of an antithromboplastin nature (directed against later stages of intrinsic thromboplastin formation and against tissue thromboplastin), was observed, while thrombin phase was unaffected. No effect was found in the fibrinolytic system tested (euglobulin lysis, UK-activated fibrinolysis, "hanging clot" method). The drug, although capable of aggregating platelets by itself at very high concentrations, showed a striking inhibitory effect, over a wide range of concentrations, both on platelet aggregation induced by ADP, epinephrine or collagen and on platelet adhesiveness to glass or collagen. Clot retraction was also clearly inhibited. PF3 availability was influenced with a peculiar two-phase behaviour dose-dependently. High concentrations showed a promoting action, while the lower were obviously inhibitory. It is suggested that the effects on platelet function may be due to an influence of the drug on cell membrane.
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PMID:In vitro effects of bencyclan on coagulation, fibrinolysis and platelet function. 1 70

Ditazole (4,5-diphenyl-2-bis-(2-hydroxyethyl)-aminoxazol) is a new drug shown to inhibit prostaglandin release from rat platelets. The present study indicates that ditazole, at doses similar to those inhibiting prostaglandin formation in rat, inhibits in vivo collagen--but not ADP-induced rat platelet aggregation. In addition, ditazole does not prolong the bleeding time in rats, but even tends to shorten it. This effect could be due to the inhibition of prostaglandin formation at the side of the vascular injury produced to induce bleeding.
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PMID:Ditazole and platelets. II. Effect of ditazole on in vivo platelet aggregation and bleeding time in rats. 1 82

The aggregating response of human platelets stored at 22 C for 72 hours has been studied. Platelets were stored as platelet-rich plasma in order to maintain the plasma pH essentially constant. The response to ADP and collagen decreased with time, but the decrease was less with relatively high concentrations of the aggregating agents. The response to the ionophore A23187 was essentially unaltered during the storage period. Synergistic aggregation with combinations of ADP, collagen and ionophore A23187 was observed with platelets stored for 72 hours under conditions where singly each of the stimuli caused little or no effect. Stored platelets underwent reversible aggregation over a wide range of ADP concentrations but irreversible aggregation was observed in the presence of nonaggregating concentrations of collagen or ionophore A23187. The inhibition of aggregation by PGE1 or cyclic AMP was facilitated as a result of storage. It is suggested that the decreased response toward ADP and collagen reflects a reduced ability on the part of the platelets to mobilize calcium.
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PMID:Aggregation response of human platelets stored at 22 C as platelet-rich plasma. 4 98

The ultrastructure and adenine nucleotide metabolism of platelets from patients with acute leukemia were studied to elucidate possible mechanisms for the platelet dysfunction observed in this clinical setting. Nonstimulated (resting) platelets from leukemic patients varied greatly in size; exhibited marked variation in the number of alpha granules present per cell; had poorly delineated circumferential bands of microtubules; and often grossly dilated open channel systems or cytoplasmic vacuolization. The intracellular concentrations of ATP and ADP were significantly below normal, and the specific radioactivity of ATP and ADP of nonstimulated platelets in leukemia was equivalent to or exceeded that seen in stimulated normal platelets. Addition of ADP or collagen to platelets from leukemic patients was followed by retarded and incomplete shape change, delayed and incomplete centripetal migration of subcellular organelles, impaired degranulation, and the formation of loose aggregates composed of relatively few platelets. Stimulation of "leukemic" platelets with collagen led to the release of significantly subnormal amounts of ATP and ADP and no significant change in the specific radioactivity of the intracellular nucleotides. In contrast to the results in normal platelets, the conversion of ATP to inosine monophosphate and hypoxanthine in platelets in leukemia failed to increase significantly with collagen stimulation. The results indicate that abnormalities exist in the storage pool of adenine nucleotides and the release mechanism of platelets in acute leukemia. These defects appear to contribute to an impairment in the release reaction in these platelets. Many of the ultrastructural and metabolic defects seen in acute leukemia occur in platelets in preleukemia.
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PMID:The platelet defect in leukemia. Platelet ultrastructure, adenine nucleotide metabolism, and the release reaction. 4 18

Multiple platelet abnormalities were found in a patient with bleeding symptoms. The platelet content of ADP and PF 4 was decreased and the uptake of 14C-serotonin was impaired. The content of acid phosphatase, beta-glucuronidase and beta-N-acetylglucosaminidase was, however, normal and these enzymes were normally released or made available by bovine fibrinogen or ADP. There was no adhesion of platelet to collagen, which also failed to induce reptilase clot retraction, platelet aggregation and release of any of the platelet constituents. The platelets therefore exhibited signs of thrombocytopathy of a combined type with a decreased storage pool as well as a qualitative dysfunction with impaired reactivity to collagen.
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PMID:A new abnormality of platelet functions. Association of storage pool disease (thrombocytopathia A) with impaired reactivity of platelets to collagen. 5 81

Gel filtration of human platelet-rich plasma (PRP) on columns of Sepharose 2B removed at least 99.85% of the plasma proteins from platelets when a column 10 cm in height was used and a plasma volume 11 to 14% of the gel-bed volume was applied. ADP and ATP levels in gel-filtered platelets (GFP) were not significantly different from those in PRP. By transmission electron microscopy, GFP were indistinguishable from PRP. Gel filtration appears to be a highly satisfactory technique of separating platelets from plasma without modifying structure, function, or contents significantly. The roles of several crude protein fractions in platelet aggregation and aspirin's inhibition of aggregation were examined. Fraction I (mostly fibrinogen) enhanced collagen-induced aggregation of gel-filtered platelets; Fraction V (mostly albumin) was inhibitory. Fraction II (mostly gamma-globulin) or gelatin had no significant effect. Aspirin added to gel-filtered platelets inhibited aggregation by 80%. The addition of mixtures of plasma proteins containing albumin increased albumin's inhibitory effect. Incubation of gel-filtered platelets with aspirin labeled in the carboxyl position resulted in no uptake of the label. In contrast, incubation with acetyl-labeled aspirin was followed by uptake of more than 2 X 10(6) acetyl groups per platelet in 1 minute. Incubation for 30 minutes resulted in a five- to sixfold further increase in uptake of the label. Aspirin can acetylate platelets and inhibit aggregation directly. Plasma proteins, in particular albumin or a contaminant of the albumin fraction tested, enhance the inhibitory effect of aspirin on platelet aggregation.
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PMID:Gel-filtered human platelets. Ultrastructure, function, and role of proteins in inhibition of aggregation by aspirin. 5 50

The ADP- and collagen-induced aggregation of platelets in PRP of healthy probands was tested in vitro in the presence of 4 heparin preparations (Novo, Vitrum, Liquemin, Haemoderivate) and of a heparinoid (Eleparon). None of the preparations caused a significant direct aggregation. The collagen-induced aggregation was inhibited by all mentioned preparations; thereby the heparins proved to be effective approx. to the same degree whereas the heparinoid proved to be significantly less effective. The ADP-induced aggregation was potentiated by all preparations. A considerably different sensitivity to heparin could be observed in the single PRP's. A special method was found out to exclude the influence of the heparin-sensitivity of the PRP's to compare the special effects of the heparins.
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PMID:[Influence of five commercial heparin preparations on the collagen induced platelet aggregation (author's transl)]. 7 75

Platelet and fibrinogen survival and turnover studies have shown that platelet activation and fibrin formation may occur to different degrees in different thrombotic disorders. More direct evidence of differential involvement of platelet activation and fibrin formation should be provided by specifically measuring the products of these reactions, i.e. released platelet proteins and fibrinopeptide A. Two platelet proteins, platelet factor 4 (PF4) and beta-thromboglobulin (betaTG), were isolated and characterized, and sensitive and specific radioimmunoassays were developed to measure them. These assays were employed, along with the radioimmunoassay for fibrinopeptide A (FPA), to study the release of PF4 and betaTG in relation to FPA cleavage. PF4 and betaTG were released by ADP and collagen with time course and concentration dependence similar to that of [14C]serotonin release. FPA was not cleaved from fibrinogen during ADP or collagen-induced platelet release. Thrombin caused release of PF4 and betaTG as well as cleavage of FPA. Cleavage of FPA occurred with concentrations of thrombin about 100 times less than did release of PF4 and betaTG, and release of [14C]serotinin required still higher thrombin concentrations. Release of [14C]serotonin and platelet proteins was similar as a function of time. Sodium citrate was found to inhibit platelet release induced by thrombin.
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PMID:Radioimmunoassay of platelet factor 4 and beta-thromboglobulin: development and application to studies of platelet release in relation to fibrinopeptide A generation. 7 21

In thrombin-induced DIC, acetylsalicylic acid (ASA) prevents the strong initial fall in platelet count and the obturation of the microvasculature of the lung with platelet aggregates. During the DIC reaction increasing inhibition of aggregability of circulating platelets against collagen and ADP is observed. Furthermore, ASA prevents the increase in the plasma haemoglobin level caused by DIC.
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PMID:[Effect of ASS on platelet function in experimental DIC]. 9 74


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