Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The phosphodiesterase (PDE) inhibitors AY-31,390, milrinone and pelrinone (AY-28,768) were analyzed in human platelet aggregatory systems and in a rabbit arteriovenous shunt model to delineate their activity. AY-31,390 showed a remarkably potent capacity to inhibit human antithrombotic platelet aggregation. AY-31,390 inhibited arachidonic acid, U46619, collagen, epinephrine (second phase) and adenosine diphosphate (second phase) induced platelet aggregation (PA) with IC50 values of 0.18, 0.21, 0.54, 0.43 and 0.20 microM, respectively. Milrinone, although less potent than AY-31,390, inhibited PA with IC50 values of 2.1, 2.0, 5.4, 3.7 and 4.1 microM and pelrinone's IC50 values were 2.8, 6.6, 13.3, 18.6 and 11.8 microM, respectively. Platelets which were incubated with AY-31,390, milrinone or pelrinone, washed with Hanks' balanced salt solution and then resuspended in platelet poor plasma, lost their inhibitory activity in collagen and arachidonic acid PA systems. These results suggested that AY-31,390, milrinone and pelrinone did not bind tightly to cAMP PDE. If human platelet-rich plasma was pretreated with adenosine deaminase, an enzyme that degrades adenosine, the inhibitory effect of milrinone and to a lesser extent pelrinone was reversed. AY-31,390 did not produce a loss of activity with adenosine deaminase in the arachidonic acid system and only a small loss in the collagen system. Adenosine did not appear to be a meaningful factor in AY-31,390's inhibitory activity. Pelrinone, milrinone to a greater extent, and AY-31,390 to the greatest extent were effective inhibitors of white thrombus formation in the in vivo rabbit arteriovenous shunt model. These PDE III inhibitors were potent deterrants of platelet aggregation and white thrombus formation; these agents would be expected to be efficacious therapeutic antithrombotics.
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PMID:Comparative antithrombotic activities of the phosphodiesterase inhibitors pelrinone (AY-26,768), AY-31,390 and milrinone. 189 59

In the present investigation, effect of rat peripheral polymorphonuclear leukocyte (PMNL) supernatant was investigated on platelet aggregation. Rat PMNLs suspended in Hanks balanced salt solution (HBSS, pH 7.4) were incubated at 37 degrees C for different time intervals and cell-free supernatant was obtained by centrifugation. Supernatant was found to inhibit adenosine diphosphate (ADP), arachidonic acid (AA), and calcium ionophore-induced platelet aggregation. The inhibitory effect of PMNL supernatant on platelet aggregation was not blocked by methylene blue (10 microM) or adenosine deaminase (5 U ml(-1)) pretreatment, suggesting that the inhibitory effect of the supernatant on aggregation was not mediated by nitric oxide (NO) or ecto-ADPase. The effect of PMNL supernatant on platelet aggregation was abolished by preheating the supernatant at 95 degrees C for 5 minutes. Pretreatment of the supernatant with protease inhibitors abolished the inhibitory effect of supernatant on platelet aggregation suggesting that the factor may be a protein or peptide with protease activity. Partial purification of biologically active factor by fine particle liquid chromatography (FPLC) by using Superose 6B column yielded a peak with a molecular weight of approximately 30 kDa having antiaggregatory activity. The results obtained suggest that rat peripheral PMNLs release yet another factor(s) that inhibits platelet aggregation. The factor is a heat labile protein with a molecular weight of approximately 30 kDa.
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PMID:Inhibition of platelet aggregation by a protein factor present in rat peripheral polymorphonuclear leukocyte supernatant. 972 23