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.
Delitala
G
G
Institute of Endocrinology and Haematology, University of Sassari, Italy.
Palermo
M
M
Tomasi
P
P
Besser
M
M
Grossman
A
A
D000311:Adrenal Glands / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D010902:Pituitary Gland / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*
D011942:Receptors, Adrenergic, alpha; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D008729:Methoxamine; D003913:Dextroamphetamine; D006854:Hydrocortisone