Effects of platelet antagonists on the reduction in platelet density caused by microbubbles in vitro.
Platelet-rich plasma (PRP) was stirred and incubated at 37 degrees C with N2 microbubbles in vitro in the presence and absence of platelet antagonists. The N2 microbubbles acted as a platelet agonist, like "classical" agonists such as ADP, collagen, and thrombin, causing an agonist-induced aggregation requiring extracellular Ca2+. This aggregation is abolished by 2-ethylamineglycolether (N',N',N',N') tetraacetate (chelator of extracellular Ca2+), and 2-deoxy-D-glucose plus antimycin A (inhibitors of glycolysis and electron transport, and thereby of ATP production). Furthermore, this aggregation could be depressed pharmacologically by several antagonists of the aggregation induced by "classical" platelet agonists. The greatest inhibition of microbubble-induced aggregation was obtained by substances that increase the intracellular levels of cyclic AMP. Medications that are in common clinical use, such as theophylline, seem promising in this respect. The prostaglandin-thromboxane pathway did not seem to be involved in the N2 microbubble-induced platelet aggregation in vitro, since acetylsalicylic acid and indomethacin were without effect, nor did the 3',5'-cyclic guanosine monophosphate pathway seem to be linked to this aggregation mechanism.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000502:physiology; D000527:Alprostadil / Q000494:pharmacology; D000968:Antimycin A / Q000031:analogs & derivatives / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000502:physiology; D016861:Cyclooxygenase Inhibitors; D003665:Decompression Sickness / Q000097:blood; D003847:Deoxyglucose / Q000494:pharmacology; D005740:Gases / Q000494:pharmacology*; D006801:Humans; D009584:Nitrogen / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D011941:Receptors, Adrenergic / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D005740:Gases; D011941:Receptors, Adrenergic; C032456:antimycin; D000244:Adenosine Diphosphate; D000968:Antimycin A; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases; D000527:Alprostadil; D009584:Nitrogen; D002118:Calcium