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Biomedical subjects

C Malmsten

Publications and source records attributed to C Malmsten.

32 records · Page 2Linked to original sources
PubMed1980

Inhibition of platelet aggregation and elevation of cyclic-AMP levels in platelets by 13,14-dehydro PGI2 methyl ester.

13,14-Dehydro PGI2 (dh-PGI2) and 13,14-dehydro PGI2 methyl ester (dh-PGI2-Me) inhibited platelet aggregation and release of [14C]-serotonin and ADP induced by collagen, ADP, arachidonic acid and PGG2. The inhibitory dose (ID50) ofg dh-PGI2-Me on platelet aggregation was 3 x 10(-9)M when induced with collagen, 2 x 10(-8) M with ADP, 5 x 10(-9) M with arachidonic acid and 1 x 10(-8)M with PGG2. The effects of dh-PGI2 and dh-POGI2-Me on platelet aggregation appear to be mediated by cyclic AMP, since both agents were potent to stimulate platelet cyclic AMP formation. In this respect dh-PGI2-Me was more effective than dh-PGI2 and PGE1. The actions of dh-PGI2-Me on platelet aggregation reported in this study suggest that is posseses similar biological properties as natural PGI2. Since dh-PGI2-Me is considerably more stable at physiological pH than PGI2 (Fried, J. and Barton, J. (1977) Proc. Natl. Acad. Sci. USA, 74, 2199-2203) this PGI2 analog might be useful as an anti-thrombotic drug.

Adenosine Diphosphate↗
PubMed1979

Further studies on a specific platelet antibody found in Bernard-Soulier syndrome and its effects on normal platelet function.

An IgG antiplatelet antibody found in a multitransfused patient with Bernard-Soulier syndrome (BSS), reacted with a normal platelet surface antigen of 150 000 daltons which was similar to the glycoprotein missing from BSS platelets. The BSS platelet antibody (BSS-Pab) aggregated all control platelets which then released ADP and 5-HT and synthesized thromboxane. When mixed with the antibody, BSS platelets did not aggregate, did not release ADP and 5-HT and failed to synthesize thromboxane. The BSS-Pab was not inactivated by incubation with BSS platelet stroma. While the antibody did not aggregate thrombasthenic platelets, its aggregating activity was lost after incubation with their stroma. The BSS-Pab did not provoke ADP or 5-HT release or thromboxane synthesis in thrombasthenic platelets or in the platelets of a patient with platelet cyclooxygenase deficiency or in normal platelets treated with indomethacin. The aggregating, release and synthetic responses of platelets after binding of BSS-Pab to its membrane antigen (probably glycoprotein I) requires the presence of glycoprotein IIb and/or IIa and the normal metabolism of arachidonic acid.

Antibodies↗
PubMed1977

On the interrelationship of prostaglandin endoperoxide G2 and cyclic nucleotides in platelet function.

The prostaglandin endoperoxide G2 caused rapid aggregation and relase of ADP and [14C]serotonin in human platelets. Since the presence of the ADP phosphorylating system creatine phosphate/creatine phosphokinase markedly inhibited the aggregation caused by the endoperoxide, this effect seemed to be mediated mainly by ADP, which is instantaneously released by the endoperoxide. The prostaglandin G2 counteracted the increasing effect of prostaglandin E1 on the adenosine 3':5'-monophosphate (cAMP) levels in platelet-rich plasma. This effect of prostaglandin G2 was only observed when ADP was released by the endoperoxide. This finding indicates that the effect of prostaglandin G2 on the cAMP levels in platelet-rich plasma is principally mediated by ADP. The rapid release of ADP by prostaglandin G2 and the time courses for the effects of the endoperoxide and ADP on the level of cAMP give further evidence for this hypothesis. ADP also caused primary aggregation in the presence of indomethacin, and prostaglandin synthesis inhibitors did not influence the decreasing effect of ADP on the cAMP levels. N2,O2-Dibutyrylguanosine 3':5'-monophosphate did not influence the aggregation and release-reaction caused by ADP and no changes of the cGMP levels were observed after addition of prostaglandin G2.

Adenosine Diphosphate↗
PubMed1975

Physiological role of an endoperoxide in human platelets: hemostatic defect due to platelet cyclo-oxygenase deficiency.

The endoperoxide prostaglandin G2 (PGG2) induced platelet aggregation as well as the platelet release reaction (release of ADP and serotonin) when added to human platelet-rich plasma. Formation of a metabolite of PGG2 [8-(l-hydroxy-3-oxopropyl)-9,12L-dihydroxy-5,10-heptadecadienoic acid] and a lipoxygenase product [12L-hydroxy-5,8,10,14-eicosatetraenoic acid] accompanied the release reaction caused by aggregating agents such as collagen, ADP, epinephrine, and thrombin. Indomethacin inhibited the release reaction and PGG2 formation induced by these agents but had no effect on PGG2-induced release reaction. The aggregating effect of PGG2 was abolished by furosemide, which is a competitive inhibitor of ADP-induced primary aggregation. These data indicate that the aggregating effect of PGG2 is due to release of ADP and that PGG2 synthesis is required for induction of the release reaction by various aggregating agents. A subject with a hemostatic defect due to abnormal release mechanism [decreased aggregation with epinephrine (second wave) and collagen and normal platelet ADP] had a deficiency of the cyclo-oxygenase that catalyzes formation of PGG2. Normal aggregation and release reaction were obtained with added PGG2. Ii is concluded that the endoperoxide (PGG2) is essential in normal hemostasis because of its role in initiating the release reaction required for aggregation by collagen and the second wave of aggregation caused by, e.g., ADP.

Adenosine Diphosphate↗