Abstract:
We investigated the effect of a new PAF antagonist pinusolide, isolated
from the leaves of Biota orientalis, on PAF-induced
[3
H]serotinin release from rabbit platelets,
hypotension and vascular permeability. Pinusolide (IC50, about
5 × 10-6 M) inhibited specifically [3
H]serotinin release from rabbit platelets when stimulated
with PAF (5 × 10-8 M), but showed no effect
when induced by ADP, collagen, and thrombin. It also inhibited PAF-induced
hypotension in a dose-dependent manner in rats with no effect on the hypotension
induced by acetylcholine, histamine and serotonin. The inhibitory effect of
pinusolide on the PAF-induced vascular permeability is less specific than
the induced hypotension. These results suggest that pinusolide may prove of
therapeutic value in the treatment of hypotension and a molecular design of
pinusolide analogues may provide the possibility of a new PAF specific antagonists.
Key words:
Biota orientalis
- Cupressaceae - pinusolide - specific PAF antagonist - hypotension - vascular permeability
in vivo