Effects of sarpogrelate hydrochloride on platelet aggregation, and its relation to the release of serotonin and P-selectin.
Inhibitory effects of sarpogrelate hydrochloride (sarpogrelate), a 5-HT2 receptor antagonist, on platelet aggregation was examined as well as the relationship to serotonin and P-selectin, a platelet alpha-granule membrane glycoprotein. Platelet aggregation was induced by simultaneous addition of collagen (0.06-0.12 microg/ml), which did not induce aggregation alone, and serotonin (0.88 micromol/1) to platelet-rich plasma (PRP). The PRP was obtained from healthy volunteers and percentage maximum aggregation (MA) was measured. Serotonin levels and P-selectin levels in the supernatant of PRP after aggregation were determined. When vehicle-treated PRP was stimulated in the aforementioned manner, platelet aggregation dependent on collagen concentration was induced. Serotonin levels and P-selectin levels were also dependent on collagen concentration. Sarpogrelate (10(-6) to 10(-4) mol/l) inhibited such aggregation dose-dependently, and decreased serotonin levels and P-selectin levels in a dose-dependent manner. There were close correlations between MA and serotonin levels, MA and P-selectin levels, as well as serotonin and P-selectin levels. These results suggest that extracellular release of serotonin and P-selectin from platelets was caused by induction of aggregation, and these responses were suppressed by sarpogrelate.
Nakamura
K
K
Department of Hospital Pharmacy, Faculty of Medicine, Kagoshima University, Japan. nakamura@khosp3.kufm.kagoshima-u.ac.jp
Kariyazono
H
H
Moriyama
Y
Y
Toyohira
H
H
Kubo
H
H
Yotsumoto
G
G
Taira
A
A
Yamada
K
K
D000328:Adult; D003094:Collagen / Q000494:pharmacology; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D012701:Serotonin / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013386:Succinates / Q000494:pharmacology*
D005343:Fibrinolytic Agents; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D012702:Serotonin Antagonists; D013386:Succinates; C064294:sarpogrelate; D012701:Serotonin; D003094:Collagen