Influence of the cGMP analog 8-PCPT-cGMP on agonist-induced increases in cytosolic ionized Ca2+ and on aggregation of human platelets.
The present study was undertaken to compare inhibitory effects of the cGMP analog 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate (8-PCPT-cGMP) on increases in cytosolic ionized Ca2+ and on aggregation in human platelets induced via diverse agonists. Fura-2-loaded and gel-filtered platelets were stimulated by either ADP (8 microM), thrombin (0.025 IU/ml) or collagen (1-3 micrograms/ml), respectively. The cGMP analog induced a concentration-dependent inhibition of cytosolic ionized Ca2+ increases and of aggregation to all agonists investigated with half-maximal inhibiting effects of approximately 100 microM. The data obtained suggest that both platelet Ca2+ exchange and aggregation have a similar sensitivity to the cGMP analog. In accordance with previously found significant differences between the potencies of nitric oxide (NO)-generating substances to inhibit increases in cytosolic ionized Ca2+ and aggregation, it appears that the antiplatelet effects of NO-releasing agents could only partially be explained by the elevation of cGMP levels.
Menshikov MYu
Abteilung für klinische Pharmakologie, Klinikum Innenstadt, Universität München, Germany.
Ivanova
K
K
Schaefer
M
M
Drummer
C
C
Gerzer
R
R
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D013873:Thionucleotides / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology
D013873:Thionucleotides; C055656:8-((4-chlorophenyl)thio)cyclic-3',5'-GMP; D000244:Adenosine Diphosphate; D003094:Collagen; D013917:Thrombin; D006152:Cyclic GMP; D002118:Calcium