| Summary: | 碩士 === 國立臺灣大學 === 藥理學研究所 === 82 === The purpose of this thesis is to investigate the mechanisms of
ellagitannins-induced platelet aggregation and the
antiprolifera- tion action of cinnamophilin, in vascular smooth
muscle cells. We found rugosin E-induced aggregaion of washed
rabbit platelets was a concentration-dependent manner with an
EC50 value of 1.5±0.1μ M. The maximal aggregation caused by
rugosin E (5μM) was 84.1± 1.1%. ADP-scavenging enzyme
systems, CP/CPK and apyrase inhibited concentration-dependently
ADP-induced platelet aggregation, with- out affecting rugosin E-
induced platelet aggregation. Selective ADP receptor
antogonists, ATP and FSBA inhibited rugosin E- and ADP-induced
platelet aggregations in a concentration-dependent manner. Both
rugosin E and ADP did not induced platelet aggrega- tion in
desensitized platelet. Both rugosin E and ADP did not induced
PI breakdown in [3H]myo-inositol-labeled rabbit platelets .
Both rugosin E and ADP-induced increase in intracellular calci-
um concentration and were inhibited by ATP and PGE1. These data
suggest that rugosin E may be a ADP receptor agonist in rabbit
platelets. U46619 selectively bound to TxA2/PGH2 receptors in
cultured vascular smooth cells of rat thoracic aorta.
Cinnamophi- lin completed with U46619 for binding to TxA2/PGH2
receptor and inhibited the following events, including U46619-
mediated cell proliferation, [3H]thymidine incorporation, PI
breakdown, cytos- olic calcium ion mobilization and increase of
total cell protein content in cultured A10 cells. In vascular
smooth muscle cell proliferation, TxA2 may play a role as a
'competence factor', but not a 'progression factor'.
Cinnamophilin and SQ29548 inhibited U46619-induced DNA and
protein systhesis, PI breakdown and cytos- olic calcium ion
mobiliztion by blocking [3H]U46619 binding to cultured vascular
smooth muscle cells. In atherosclerosis, TxA2 may induce
vascular smooth muscle hypertrophy, not hyperplasia.
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