Inhibitory effects of S-(1,2-dicarboxyethyl)glutathione on collagen-induced platelet aggregation; enhancements of cyclic AMP level and adenylate cyclase activity in platelets by S-(1,2-dicarboxyethyl)glutathione.
S-(1,2-Dicarboxyethyl)glutathione (DCE-GS) in addition to being present in the liver, lens, and heart, also inhibited platelet aggregation. To clarify these inhibitory effects, the role of DCE-GS in the release of ATP and serotonin from platelets was studied, as was thromoboxane A2 formation, cyclic AMP level and adenylate cyclase activity in human platelets. The results are as follows: DCE-GS at a concentration of 1.3 mM inhibited ATP and serotonin release from platelets induced by collagen, by 77.4 +/- 4.3 and 78.7 +/- 6.3%, respectively. At 1.5 mM DCE-GS also inhibited the formation of thromboxane B2 by 79.6 +/- 4.1%. Incubation of human platelet rich plasma with 2 mM of DCE-GS for 10 min increased the cyclic AMP level and the activity of adenylate cyclase by 204 +/- 28 and 211 +/- 11.7%, respectively. These results suggest that the inhibitory effect of DCE-GS on the platelet aggregation induced by collagen is due to an increase in the cyclic AMP level in platelets, which in turn may be due to enhancement of the activity of adenylate cyclase.
Tsuboi
S
S
Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Fujiwara
E
E
Ogata
K
K
Sakaue
A
A
Nakayama
T
T
Ohmori
S
S
D000255:Adenosine Triphosphate / Q000097:blood; D000262:Adenylyl Cyclases / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D012701:Serotonin / Q000097:blood; D013928:Thromboxane A2 / Q000096:biosynthesis
D010975:Platelet Aggregation Inhibitors; C041581:S-(1,2-dicarboxyethyl)glutathione; D012701:Serotonin; D013928:Thromboxane A2; D000255:Adenosine Triphosphate; D003094:Collagen; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D005978:Glutathione