Release of specific polyunsaturated fatty acids from cell membranes ma
y have a significant implication in biological function, considering t
he involvement of various fatty acids in cell signal transduction. In
the present study, release of polyunsaturated fatty acids from rat bra
in synaptosomes by endogenous synaptosomal lipase activity was examine
d in comparison to that by cobra venom phospholipase A(2) (Naja naja n
aja). Cobra venom phospholipase A(2) (Naja naja naja) preferentially h
ydrolyzed docosahexaenoic acid (22:6n-3) from both synaptosomes and li
pid mixtures containing similar classes of lipids commonly found in th
e brain. Arachidonic acid (20:4n-6) and oleic acid (18:1n-9) were also
hydrolyzed; however, monoene species was hydrolyzed slower than were
polyenoic species in synaptosomes. Phosphatidylethanolamine was the mo
st preferred phospholipid class for release of 22:6n-3 fatty acid from
both lipid mixtures and synaptosomes. In contrast to hydrolysis by co
bra venom phospholipase A(2), endogenous synaptosomal lipase activity
preferentially hydrolyzed 20:4n-6 from rat brain synaptosomes, despite
the high abundance of 22:6n-3 in synaptosomal membranes. Preferential
release of 20:4n-6 was observed over a wide range of pH values and ca
lcium concentrations. Synaptosomal 22:6 species appeared to be resista
nt to hydrolysis even after stimulation with various agents such as ph
orbolmyristate, suggesting that physiological importance of 22:6n-3 in
neuronal membranes may not be as the release fatty acid.