EFFECTS OF OPIOID DRUGS AND OF LITHIUM ON STEROIDOGENESIS IN RAT ADRENAL-CELL SUSPENSIONS

The effects of opioid drugs and of Na+ replacement on steroidogenesis in rat adrenal cell suspensions were investigated. In medium containing normal Na+ (156 mm), opioid antagonists but not opioid agonists reduced the steroidogenic response to adrenocorticotrophic hormone1–24. (ACTH1–24) but not to dibutyryl adenosine 3′,5′ cyclic monophosphate (db cyclic AMP). Replacement of 50% Na+ in the medium by choline had no effect on steroidogenesis, but further reductions in Na+ content reduced the steroidogenic activity of both ACTH1–24 and db cyclic AMP. In 50% Na+ medium both opioid agonists and antagonists inhibited ACTH1–24 induced steroidogenesis. Addition of therapeutic concentrations of lithium to otherwise normal medium inhibited the steroidogenic response to ACTH1–24 but not to db cyclic AMP. The selective inhibition of ACTH1–24‐induced steroidogenesis by opioid drugs suggests some similarity between the opioid and ACTH receptors. The relevance of the potent inhibitory effect of lithium to its therapeutic actions is discussed. 1979 British Pharmacological Society