Modulation of calcium-dependent neutral protease activity by fatty acids and lysophospholipids

The effect of fatty acids and lysophospholipids on calcium-activated neutral protease (CANP) was investigated. mu CANP, low calcium ion (microM concentration)-requiring CANP is more strongly inhibited by unsaturated fatty acids than is mCANP--the high calcium ion (mM concentration)-requiring form. Lysophospholipids in concentrations ranging from 10(-5) M to 10(-3) M inhibit mu CANP exclusively, whereas mCANP activity is unaffected or even slightly increased. Calpastatin decreases the activity of mCANP and, in the presence of polyunsaturated fatty acids such as docosahexaenoic acid, the inhibition is not increased. In the presence of lysophosphatidyl-ethanolamine, however, the inhibition of mCANP by calpastatin does not occur. The results indicate that fatty acids and lysocompounds liberated under different physiological and pathological conditions may modulate calcium-activated neutral protease.