Adrenergic stimulation of the human pituitary-adrenal axis is attenuated by an analog of met-enkephalin.

It has previously been suggested that endogenous opioid peptides may suppress the pituitary-adrenal axis in man by inhibiting an excitatory alpha 1-adrenoceptor input to neural mechanisms liberating corticotrophin-releasing factor or factors (CRFs). This hypothesis has been tested here by investigating the effect of the met-enkephalin analog, DAMME (FK-33,824), on the elevation in serum cortisol induced by the catecholamine-releasing agent d-amphetamine (10 and 25 mg p.o.) and the direct alpha 1-adrenoceptor agonist methoxamine (6 micrograms/kg/min i.v.) in two groups of 6 normal male subjects. In both studies, the rise in serum cortisol was significantly attenuated by the analog of met-enkephalin. These data suggest that exogenous opioids act as a site downstream to the alpha 1-adrenoceptor input to CRF release; it appears that opioids modulate adrenocorticotrophic hormone release in man at a minimum of two distinct and separate sites. Z9 16