Prostaglandins and Cannabis—VIII. Elevation of Phospholipase A₂ Activity by Cannabinoids in Whole Cells and Subcellular Preparations

Abstract

The previously reported release of arachidonic acid by THC has now been demonstrated in murine Leydig cells and WI‐38 human lung fibroblasts showing the generality of the effect. The release reaction could be antagonized by phospholipase A2 inhibitors such as quinacrine and quinine, suggesting that THC can stimulate the activity of this enzyme. Further evidence for this possibility was obtained by demonstrating the release effect on a subcellular fraction which contained the phospholipase A2 activity. The stimulation of this enzyme could have profound effects on prostaglandin synthesis and/or on the integrity of various membrane structures.

Role of Prostaglandins in Marihuana-Induced Bronchodilation

“…Marihuana produced a significant bronchodilation and tachycardia similar to those reported elsewhere [1,2], If these effects were mediated by prostaglandins they could possibly be blocked by quinacrine, as demonstrated by Burstein and Hunter [9] in vitro, or by cyclooxygenase inhibitors. In their experiments, Burstein and Hunter [9] used a high concentration of quinacrine: 47.2 jug/ml.…”

“…They recently reported that in cell cultures the THC-induced PG synthesis was blocked by quinacrine; this substance has been shown to inhibit phospholipase A2 activity [11,12]. They suggest that THC induces PG pro duction by stimulating phospholipase A2 which releases arachidonic acid from the cellular phospholipids [9]. There is no in vivo study to confirm this possibility.…”

“…In their experiments, Burstein and Hunter [9] used a high concentration of quinacrine: 47.2 jug/ml. According to the known pharmacology of this drug, the therapeutic doses prescribed for giardiasis would not allow to reach more than 5% of that value in volunteers' lungs [17].…”

“…For example THC blocks the arachidonic acid-induced rise of intraocular pressure in rabbits, while PGE2 overrides this effect and increases the intraocular pressure [8]. There are many other studies which, depending on the methodology, re port either a stimulation of PG production or its inhibition by THC [9].…”

Decrease in Efficacy and Potency of Nonsteroidal Anti-Inflammatory Drugs by Chronic Δ9-Tetrahydrocannabinol Administration

“…The present study is based upon previous work that indicate that acute administration of cannabinoids stimulates the release of arachadonic acid resulting in elevation of prostaglandins (Burstein and Hunter, 1981;Burstein et al, 1983;Laviolette and Belanger, 1986;Bhattacharya, 1986;Hunter et al, 1991). Furthermore, cannabinoids induce COX-2 expression in the central nervous system (Ramer et al, 2001).…”