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Effects of cannabinoids on the activities of mouse brain lipases

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Abstract

Cannabinoids were found to augment phospholipase activities and modify lipid levels of mouse brain synaptosomes, myelin and mitochondria. Delta-1-tetrahydrocannabinol (Δ1-THC) and several of its metabolites induced a dose-dependent (0.32–16 μM) stimulation of phospholipase A2 (PLA2) activity resulting in the increased release of free arachidonic acid from exogenous [1-14C]phosphatidylcholine (PC). The potencies of the cannabinoids in modulating PLA2 activity were approximately of the order: 7-OH-Δ1-THC > Δ1-THC > 7-oxo-Δ1-THC > Δ1-THC-7oic acid = 6α OH-Δ1-THC ≫ 6β-OH-Δ1-THC. The hydrolysis of phosphatidylinositol (PI) by synaptosomal phospholipase C (PLC) was enhanced significantly by Δ1-THC and promoted diacylglyceride levels by greater than 100 percent compared to control values. In contrast, arachidonate was the major product resulting from phospholipase activities of a 20,000g pellet. Synaptosomal diacylglyceride lipase activity was inhibited by Δ1-THC. [1-14C]Arachidonic acid was readily incorporated into subcellular membrane phospholipids and after exposure to cannabinoids led to diminished phosphoglyceride levels and concomitant increases in released neutral lipid products. These data suggest that cannabinoids control phospholipid turnover and metabolism in mouse brain preparations by the activation of phospholipases and, through this mechanism, may exert some of their effects.

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  1. Department of Biochemistry, University of Massachusetts Medical School, 01605, Worcester, Massachusetts

    Sheila A. Hunter, Sumner Burstein & Lori Renzulli

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  1. Sheila A. Hunter
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  2. Sumner Burstein
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  3. Lori Renzulli
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Hunter, S.A., Burstein, S. & Renzulli, L. Effects of cannabinoids on the activities of mouse brain lipases. Neurochem Res 11, 1273–1288 (1986). https://doi.org/10.1007/BF00966122

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