Thromboxane receptor stimulation inhibits adenylate cyclase and reduces cyclic AMP-mediated inhibition of ADP-evoked responses in fura-2-loaded human platelets.
Stimulation of human platelets with the thromboxane A2 analogue, U46619, after treatment with prostaglandin E1 or forskolin, reduced the inhibition of ADP-evoked Mn2+ influx and the release of Ca2+ from intracellular stores. U46619 decreased the elevated concentration of 3',5'-cyclic AMP in platelets that were pretreated with prostaglandin E1. These results suggest that occupation of prostaglandin H2/thromboxane A2 receptors, like those for other agonists, inhibits adenylate cyclase activity, which can contribute to the promotion of platelet activation.
Sage
S O
SO
Physiological Laboratory, University of Cambridge, UK.
Heemskerk
J W
JW
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors / Q000502:physiology; D000067956:Adenylyl Cyclase Inhibitors; D000527:Alprostadil / Q000037:antagonists & inhibitors*; D002118:Calcium / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D016257:Fura-2; D006801:Humans; D008345:Manganese / Q000378:metabolism; D015539:Platelet Activation; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D017482:Receptors, Thromboxane; D013928:Thromboxane A2 / Q000378:metabolism*
D000067956:Adenylyl Cyclase Inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D005576:Colforsin; D008345:Manganese; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D000242:Cyclic AMP; D000527:Alprostadil; D002118:Calcium; D016257:Fura-2