The
edema-producing activity of NNAVPLA2, an acidic
phospholipase A2 (PLA2)
enzyme from Naja naja atra
venom (NNAV), was less potent than that of
TMVPLA2 II, a basic PLA2 from
Trimeresurus mucrosquamatus venom (TMV). These
edema-forming effects were greatly suppressed by pretreatment of rats with
diphenhydramine/
methysergide or
compound 48/80, which reduced the tissue content of
histamine and
serotonin.
Heparin abolished and suppressed the paw
edema caused by
protamine and
TMVPLA2 II, respectively, but had no effect on the NNAVPLA2-induced response. In isolated rat peritoneal mast cells, both PLA2 concentration dependently induced the release of
histamine and
beta-glucuronidase. Again,
TMVPLA2 II was more potent than NNAVPLA2. This degranulation effect of mast cells caused by
TMVPLA2 II and
protamine was inhibited by
heparin, while that caused by NNAVPLA2 was unaffected. The
edema-forming and mast cell degranulation effects were greatly decreased in both PBPB-modified NNAVPLA2 and PBPB-modified
TMVPLA2 II, in which the catalytic activity of the
enzymes was completely lost. PBPB-modified
TMVPLA2 II-induced paw
edema was also suppressed by
heparin. Furthermore, this edematous response was totally reversed in rat pretreated with
aspirin in combination with
diphenhydramine and
methysergide. These results suggest that the
edema-forming effect of PLA2 is probably dependent on the presence of catalytic, positive charge and pharmacological sites on its molecule.