Biochemical interactions of ethanol with the arachidonic acid cascade.

A rapidly increasing scientific literature now supports the possibility of an alcohol-prostaglandin interaction. This chapter reviews evidence for both direct and indirect biochemical interactions between ethanol and the metabolism of arachidonic acid and several related compounds. Much of the present data is based on pharmacological manipulation of prostaglandin (PG) levels by potent nonsteroid anti-inflammatory agents such as indomethacin. Indomethacin markedly alters the behavioral response to ethanol, particularly in the mouse model. These data suggest that PGs are involved in the behavioral response to acute ethanol exposure in the mouse. In other animal models, alcohol has been reported to alter blood platelet metabolism of arachidonic acid, to suppress the enzymatic degradation of PGs, and to alter the response of the adenyl cyclase system to several hormones including PGs of the "E" series. In humans, both the stimulation and inhibition of PG synthesis is reported to aid the treatment of various aspects of alcoholism. Further, PGs are reported to protect against alcohol-induced fatty liver, and both PGs and arachidonic acid protect the gastric mucosa against ethanol-induced lesions. Certainly the residual consequences of acute, excessive ethanol consumption are commonly treated with a prostaglandin synthesis inhibitor. The material in this chapter is an attempt to review the data and to discuss the molecular mechanism underlying these observations.