Cyclic AMP does not inhibit collagen-induced platelet signal transduction.
The adhesion of platelets to collagen and their activation is the primary event in haemostasis. Following adhesion, platelet aggregation mediated by ADP, thromboxane A2 and thrombin leads to the formation of a platelet plug. It is known that platelet activation by each of these agonists involves an increase in the cytosolic free Ca2+ concentration, and this has been thought to be controlled by cyclic AMP. However, we report here that while signal transduction induced by ADP plus a thromboxane mimetic (U46619), or by thrombin, is inhibited by stimulators of adenylate cyclase such as a prostaglandin I2 (PGI2) analogue (Iloprost), PGD2 and forskolin, elevation of cyclic AMP does not inhibit either platelet adhesion to collagen or the associated Ca2+ mobilization, phosphatidic acid formation or 5-hydroxytryptamine secretion. Furthermore, collagen did not lower elevated levels of cyclic AMP in platelets measured in the presence of both a thromboxane antagonist and an ADP-removing system. The present results are discussed in the context of previous findings.
Smith
J B
JB
Department of Pharmacology, Temple University Medical School, Philadelphia, PA 19140.
Dangelmaier
C
C
Selak
M A
MA
Ashby
B
B
Daniel
J
J
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D003094:Collagen / Q000494:pharmacology*; D000242:Cyclic AMP / Q000097:blood / Q000494:pharmacology*; D005456:Fluorescent Dyes; D016257:Fura-2; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects; D015230:Prostaglandin D2 / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D012701:Serotonin / Q000097:blood; D015398:Signal Transduction / Q000187:drug effects*; D013917:Thrombin / Q000494:pharmacology
D005456:Fluorescent Dyes; D011450:Prostaglandin Endoperoxides, Synthetic; D012701:Serotonin; D000244:Adenosine Diphosphate; D003094:Collagen; D000242:Cyclic AMP; D013917:Thrombin; D016285:Iloprost; D015230:Prostaglandin D2; D002118:Calcium; D016257:Fura-2