The effects of opioid drugs and of Na+ replacement on steroidogenesis in rat adrenal cell suspensions were investigated. 2. 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). 3. 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. 4. In 50% Na+ medium both opioid agonists and antagonists inhibited ACTH1-24 induced steroidogenesis. 5. Addition of therapeutic concentrations of lithium to otherwise normal medium inhibited the steroidogenic response to ACTH1--24 but not to db cyclic AMP. 6. The selective inhibition of ACTH1--24-induced steroidogenesis by opioid drugs suggests some similarity between the opioid and ACTH receptors. 7. The relevance of the potent inhibitory effect of lithium to its therapeutic actions is discussed.
