Elevated plasma concentration of NO and cGMP may be responsible for the decreased platelet aggregation and platelet leukocyte conjugation in platelets hypo-responsive to catecholamines.
Impaired responsiveness to epinephrine and other catecholamines (CA) were previously reported in platelets of 20 approximately 30% healthy Japanese and Koreans. In the present study, the possible mechanisms of different responsiveness to CA in platelets of CA hypo-responders (CA-HY) and CA good-responders (CA-GR) were investigated. Increased platelet-leukocyte conjugate (PLC) formations were observed with whole blood of CA-GR than with that of CA-HY in both non-stimulated [mean fluorescence intensity (MFI) values: 1.33 +/- 0.26 vs. 1.16 +/- 0.19] and ADP (MFI: 5.54 +/- 3.46 vs. 2.15 +/- 1.13) or TRAP (MFI: 5.11 +/- 2.32 vs. 3.38 +/- 1.47) activated states. The platelets of CA-GR, when stimulated with ADP (10 microM), released approximately twice the amount of ATP than those of CA-HY (0.88 +/- 0.65 and 0.45 +/- 0.36 nmole, respectively). Nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels were significantly higher in non-stimulated PRP of CA-HY than in that of CA-GR (70.3 +/- 24.1 microM and 14.1 +/- 4.9 nM vs. 41.1 +/- 15.8 microM and 6.7 +/- 2.4 nM, respectively). The platelet-monocyte conjugation induced with either ADP or TRAP was significantly reduced in CA-GR with the addition of linsidomine, a NO donor, (MFI: 2.78 +/- 0.43 vs. 3.73 +/- 0.90, or 4.28 +/- 0.95 vs. 5.76 +/- 1.33, respectively). Moreover, the degree of platelet aggregation and the ATP secretion induced by epinephrine in CA-GR were significantly retarded with the addition of either linsidomine or 8-Bromo-cGMP (a cGMP analog) with more substantial effects on ATP release than aggregation. The results suggested that elevated NO and/or cGMP plasma levels may be responsible for the lower platelet aggregation and PLC formation observed in CA-HY than that in CA-GR.
Koo
Yean Kyoung
YK
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
Kim
Jeong Mi
JM
Kim
Sun Young
SY
Koo
Ja Yong
JY
Oh
Doyeun
D
Park
Seonyang
S
Yun-Choi
Hye Sook
HS
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D044466:Asian People; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002395:Catecholamines / Q000494:pharmacology*; D000242:Cyclic AMP / Q000097:blood; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000097:blood* / Q000378:metabolism; D005260:Female; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood*; D009573:Nitrites / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D055815:Young Adult
D002395:Catecholamines; D009566:Nitrates; D009573:Nitrites; D010975:Platelet Aggregation Inhibitors; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; C002385:linsidomine; D000255:Adenosine Triphosphate; D008981:Molsidomine; D000242:Cyclic AMP; D017493:Leukocyte Common Antigens; D006152:Cyclic GMP