Metabolism of arachidonic acid and prostaglandins in the torpedo electric organ: Modulation by the presynaptic muscarinic acetylcholine receptor

We have found that Torpedo electric organ readily synthesizes prostaglandin E₂ from both exogenous and endogenous arachidonate and that activation of the presynaptic muscarinic acetylcholine receptor increases the rate of prostaglandin E₂ synthesis by inducing the release of tissue arachidonate from its phospholipid pools. The incorporation of radiolabeled arachidonate into tissue phospholipids is slow and Ca²⁺ independent. However, the electric organ slices readily oxidize the externally added, radiolabeled arachidonate via the cyclo-oxygenase pathway, with prostaglandin E₂ being the major product (22 ± 4% of the initial radioactivity). This process is not affected by either Ca²⁺ or mepacrine. Torpedo electric organ slices also synthesize prostaglandin E₂ from endogenous substrates, and release it into the medium. This process, however, is enhanced by Ca²⁺ and inhibited by mepacrine. Activation of the Torpedo muscarinic acetylcholine receptor by the agonist oxotremorine results in a dose-dependent atropine-sensitive increase in the synthesis of prostaglandin E₂ from endogenous tissue substrates and in the concomitant release of arachidonate into the medium. By contrast, oxotremorine has no effect on either the formation of [¹⁴C]prostaglandin E₂ from exogenous arachidonate, the incorporation of radiolabeled arachidonate into tissue phospholipids or its liberation from prelabeled slices. These results suggest that activation of the muscarinic acetylcholine receptor induces lipolysis which results in the liberation of endogenous arachidonate and its subsequent conversion to prostaglandin E₂.