Exocannabinoids As Agonists In Pg Synthesis In vitro preparations

As mentioned above, under certain conditions the primary cannabinoids (THC, CBD etc.) and some of their metabolites inhibit the synthesis of eicosanoids. However, in most instances where systems were exposed to cannabinoids stimulatory effects were observed. The basis of these actions seems to reside in the ability of cannabinoids to mobilize phospholipid bound arachidonic acid, which then enters the cascade of reactions leading to various eicosanoids (Figure 14.2). This suggests either a direct or indirect action of these cannabinoids on one or more of the cellular phospholipases. Several reports using subcellular preparations with phospholipase activity have been published that lend support to this hypothesis (Burstein and Hunter, 1981b; Hunter etal., 1984, 1986; Evans et al., 1987). The activation of phospholipases is generally considered to be a major physiological control point for the regulation of tissue levels of eicosanoids in response to inflammatory and other stimuli. Thus, the cannabinoids would be another example of a class of agonists for this process.

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