On the antagonism by methadone of adrenocorticotropin stimulated steroidogenesis and adenosine 3', 5' cyclic monophosphate formation in isolated adrenocortical cells



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Methadone has been shown to inhibit ACTH stimulated steroidogenesis in an isolated single cell preparation from rat adrenal cortex. This effect appears to be expressed prior to progesterone in the biosynthetic pathway leading to corticosterone. Analysis of the ED[lowered 50] for methadone inhibition of cAMP production indicates that this event is not rate determining. This is supported by data obtained from an ACTH analog which ellicits no measureable cAMP and yet shows an identical ED[lowered 50] seen in the case of ACTH itself. Steroidogenesis stimulated by dbcAMP is inhibited in a like manner as that seen during ACTH stimulation. However the ED[lowered 50] of the competition differed. Finally, analysis of any in vivo implications of these observation must consider the fact that morphine was without effect in this preparation.