Properties and regulation of human platelet cation channels.
The stimulation of calcium influx by various human platelet agonists which differ in their activation pathways was investigated. ADP activates a receptor-operated cation channel (ROC) and stimulates a phospholipase C (PLC)/inositol-trisphosphate (IP3)-mediated calcium mobilization associated with a secondary calcium influx. Thrombin only stimulates the PLC/IP3-mediated calcium mobilization and associated calcium influx, perhaps followed by an additional phase of calcium influx. The platelet calcium response after incubation with the thromboxane A2 mimetic U 46619 is similar but more transient compared to that after thrombin stimulation. Tert-butylhydroquinone (an inhibitor of endoplasmatic reticulum Ca(2+)-ATPases and cyclooxygenase) elevates cytosolic calcium levels by emptying intracellular calcium stores and stimulates a biphasic calcium influx. Activation of platelet cAMP- and cGMP-dependent protein kinases inhibits the ADP- and thrombin-evoked, calcium store-associated cation influx, but not the fast receptor operated cation influx induced by ADP. Experiments with various ADP-analogs, ATP and ATP-gamma-S suggest that two different ADP-receptors may mediate the calcium responses in human platelets.
Geiger
J
J
Medizinische Universitätsklinik, Klinische Forschergruppe, Würzburg, FRG.
Walter
U
U
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000097:blood*; D002412:Cations / Q000097:blood; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000097:blood; D008954:Models, Biological; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011494:Protein Kinases / Q000097:blood; D013917:Thrombin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D010738:Type C Phospholipases / Q000097:blood; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002412:Cations; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; C022571:adenosine 5'-O-(3-thiotriphosphate); D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D010738:Type C Phospholipases; D013917:Thrombin; D002118:Calcium